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1.
Front Immunol ; 15: 1362152, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835768

RESUMO

Introduction: The effector function of T cells is regulated via immune checkpoints, activating or inhibiting the immune response. The BTLA-HVEM complex, the inhibitory immune checkpoint, may act as one of the tumor immune escape mechanisms. Therefore, interfering with the binding of these proteins can prove beneficial in cancer treatment. Our study focused on peptides interacting with HVEM at the same place as BTLA, thus disrupting the BTLA-HVEM interaction. These peptides' structure and amino acid sequences are based on the gD protein, the ligand of HVEM. Here, we investigated their immunomodulatory potential in melanoma patients. Methods: Flow cytometry analyses of activation, proliferation, and apoptosis of T cells from patients were performed. Additionally, we evaluated changes within the T cell memory compartment. Results: The most promising compound - Pep(2), increased the percentages of activated T cells and promoted their proliferation. Additionally, this peptide affected the proliferation rate and apoptosis of melanoma cell line in co-culture with T cells. Discussion: We conclude that the examined peptide may act as a booster for the immune system. Moreover, the adjuvant and activating properties of the gD-derived peptide could be used in a combinatory therapy with currently used ICI-based treatment. Our studies also demonstrate that even slight differences in the amino acid sequence of peptides and any changes in the position of the disulfide bond can strongly affect the immunomodulatory properties of compounds.


Assuntos
Ativação Linfocitária , Melanoma , Receptores Imunológicos , Membro 14 de Receptores do Fator de Necrose Tumoral , Linfócitos T , Humanos , Melanoma/imunologia , Melanoma/tratamento farmacológico , Receptores Imunológicos/metabolismo , Receptores Imunológicos/imunologia , Membro 14 de Receptores do Fator de Necrose Tumoral/metabolismo , Membro 14 de Receptores do Fator de Necrose Tumoral/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Feminino , Masculino , Pessoa de Meia-Idade , Proliferação de Células/efeitos dos fármacos , Idoso , Linhagem Celular Tumoral , Adulto , Apoptose/efeitos dos fármacos , Peptídeos/farmacologia , Peptídeos/imunologia , Gangliosídeos/imunologia
2.
Cancer Rep (Hoboken) ; 7(6): e2085, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837682

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Long noncoding RNA (lncRNA) is involved in many malignant tumors. This study aimed to clarify the role of the lncRNA plasmacytoma variant translocation 1 (PVT1) in CRC growth and metastasis. METHODS: Differentially expressed lncRNAs in CRC were analyzed using the Cancer Genome Atlas. Gene expression profiling interactive analysis and a comprehensive resource for lncRNAs from cancer arrays databases were used to analyze lncRNA PVT1 expression and CRC prognosis, respectively. Cell counting kit-8, wound healing, colony formation, Transwell, and immunofluorescence assays were used to evaluate CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), respectively. Tumor growth and metastasis models were used to explore the PVT1 effect on the growth and metastasis of CRC in vivo. RESULTS: PVT1 was highly expressed in CRC, associated with a poor prognosis of CRC, and showed good diagnostic value. Transfection of sh-PVT1 or pcDNA3.1-PVT1 reduced or increased the proliferation, wound healing rate, colony formation, invasion, and EMT of CRC cells. PVT1 and miR-3619-5p were co-expressed in CRC cytoplasm, and PVT1 acted as a competitive endogenous RNA (ceRNA) by sponging miR-3619-5p to up-regulate tripartite motif containing 29 (TRIM29) expression. MiR-3619-5p overexpression and TRIM29 knockdown reduced proliferation, wound healing rate, invasion, and EMT of CRC cells. However, simultaneous PVT1 and miR-3619-5p overexpression or knockdown of miR-3619-5p and TRIM29 knockdown rescued the malignant phenotype of CRC cells. CONCLUSIONS: We first clarified the ceRNA mechanism of PVT1 in CRC, which induced growth and metastasis by sponging with miR-3619-5p to regulate TRIM29.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , MicroRNAs , RNA Longo não Codificante , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , RNA Longo não Codificante/genética , MicroRNAs/genética , Proliferação de Células/genética , Camundongos , Animais , Prognóstico , Transição Epitelial-Mesenquimal/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Masculino , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Camundongos Nus , Feminino , Linhagem Celular Tumoral , Metástase Neoplásica , Camundongos Endogâmicos BALB C , Ensaios Antitumorais Modelo de Xenoenxerto
3.
PLoS One ; 19(6): e0303134, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38837975

RESUMO

In recent years, a cancer research trend has shifted towards identifying novel therapeutic compounds from natural assets for the management of cancer. In this study, we aimed to assess the cytotoxic activity of Kigelia Africana (KA) extracts on breast cancer (MDA-MB-231 and MCF-7) and noncancerous kidney cells (HEK-293T) to develop an efficient anticancer medication. We used gas chromatography mass spectrometry (GC-MS to analyze the constituents of EKA and HKA extracts meanwhile the crystal violet and the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays were used to examine the possible cytotoxic effects of plant extracts on our cancer cell lines along with non-cancerous control. The quantitative real-time PCR (RT-PCR) was run on cell samples to evaluate the differential expression of cell proliferative markers of cancer (BCL-2 and TP53). These phytochemicals have been reported to have binding affinity for some other growth factors and receptors as well which was evaluated by the in-silico molecular docking against Bcl2, EGFR, HER2, and TP53. Our Morphological observation showed a significant difference in the cell morphology and proliferation potential which was decreased under the effect of plant extracts treatment as compared to the control samples. The ethanol extract exhibited a marked antiproliferative activity towards MDA-MB-231 and MCF-7 cell lines with IC50 = 20 and 32 µg/mL, respectively. Quantitative RT-PCR gene expression investigation revealed that the IC50 concentration of ethanolic extract regulated the levels of mRNA expression of apoptotic genes. With the target and active binding site amino acids discovered in the molecular docking investigation, TP53/Propanoic acid, 3-(2, 3, 6-trimethyl-1, 4-dioxaspiro [4.4] non-7-yl)-, methyl ester (-7.1 kcal/mol) is the best-docked ligand. The use of this plant in folk remedies justifies its high in vitro anti-cancer capabilities. This work highlights the role of phytochemicals in the inhibition of cancer proliferation. Based on all these findings, it can be concluded that EKA extract has promising anti-proliferative effect on cancerous cells but more study is required in future to further narrow down the active ingredients of total crude extract with specific targets in cancer cells.


Assuntos
Simulação de Acoplamento Molecular , Extratos Vegetais , Proteína Supressora de Tumor p53 , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Células MCF-7 , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Feminino , Células HEK293 , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
4.
Front Immunol ; 15: 1371831, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840910

RESUMO

Introduction: Lung cancer, with the highest global mortality rate among cancers, presents a grim prognosis, often diagnosed at an advanced stage in nearly 70% of cases. Recent research has unveiled a novel mechanism of cell death termed disulfidptosis, which is facilitated by glucose scarcity and the protein SLC7A11. Methods: Utilizing the least absolute shrinkage and selection operator (LASSO) regression analysis combined with Cox regression analysis, we constructed a prognostic model focusing on disulfidptosis-related genes. Nomograms, correlation analyses, and enrichment analyses were employed to assess the significance of this model. Among the genes incorporated into the model, CHRNA5 was selected for further investigation regarding its role in LUAD cells. Biological functions of CHRNA5 were assessed using EdU, transwell, and CCK-8 assays. Results: The efficacy of the model was validated through internal testing and an external validation set, with further evaluation of its robustness and clinical applicability using a nomogram. Subsequent correlation analyses revealed associations between the risk score and infiltration of various cancer types, as well as oncogene expression. Enrichment analysis also identified associations between the risk score and pivotal biological processes and KEGG pathways. Our findings underscore the significant impact of CHRNA5 on LUAD cell proliferation, migration, and disulfidptosis. Conclusion: This study successfully developed and validated a robust prognostic model centered on disulfidptosis-related genes, providing a foundation for predicting prognosis in LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Nomogramas , Receptores Nicotínicos , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Prognóstico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Receptores Nicotínicos/genética , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Proteínas do Tecido Nervoso/genética , Linhagem Celular Tumoral , Masculino , Proliferação de Células/genética , Feminino
5.
Clin Exp Pharmacol Physiol ; 51(7): e13900, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38843865

RESUMO

Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.


Assuntos
Proliferação de Células , Medicamentos de Ervas Chinesas , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares , Neoplasias de Mama Triplo Negativas , Animais , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Camundongos , Proliferação de Células/efeitos dos fármacos , Feminino , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia
6.
J Environ Sci (China) ; 145: 1-12, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38844310

RESUMO

The potential association between colorectal cancer (CRC) and environmental pollutants is worrisome. Previous studies have found that some perfluoroalkyl acids, including perfluorooctane sulfonate (PFOS), induced colorectal tumors in experimental animals and promoted the migration of and invasion by CRC cells in vitro, but the underlying mechanism is unclear. Here, we investigated the effects of PFOS on the proliferation and migration of CRC cells and the potential mechanisms involving activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition (EMT). It was found that PFOS promoted the growth and migration of HCT116 cells at non-cytotoxic concentrations and increased the mRNA expression of the migration-related angiogenic cytokines vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). In a mechanistic investigation, the up-stream signal pathway PI3K/Akt-NF-κB was activated by PFOS, and the process was suppressed by LY294002 (PI3K/Akt inhibitor) and BAY11-7082 (NF-κB inhibitor) respectively, leading to less proliferation of HCT116 cells. Furthermore, matrix metalloproteinases (MMP) and EMT-related markers were up-regulated after PFOS exposure, and were also suppressed respectively by LY294002 and BAY11-7082. Moreover, the up-regulation of EMT markers was suppressed by a MMP inhibitor GM6001. Taken together, our results indicated that PFOS promotes colorectal cancer cell migration and proliferation by activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition. This could be a potential toxicological mechanism of PFOS-induced malignant development of colorectal cancer.


Assuntos
Ácidos Alcanossulfônicos , Movimento Celular , Neoplasias Colorretais , Transição Epitelial-Mesenquimal , Fluorocarbonos , Fluorocarbonos/toxicidade , Ácidos Alcanossulfônicos/toxicidade , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Colorretais/patologia , Humanos , Movimento Celular/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Células HCT116 , Proteínas Proto-Oncogênicas c-akt/metabolismo , NF-kappa B/metabolismo , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral
7.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(5): 496-502, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38845496

RESUMO

OBJECTIVE: To analyze the impact of cecal ligation and puncture (CLP)-induced sepsis on the proliferation and differentiation of intestinal epithelial cells. METHODS: (1) Animal experiment: sixteen male C57BL/6 mice were divided into sham operation group (Sham group) and CLP-induced sepsis model group (CLP group) by random number table method, with 8 mice in each group. After 5 days of operation, the jejunal tissues were taken for determination of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) and intestinal alkaline phosphatase (IAP) by polymerase chain reaction (PCR). The translation of LGR5 was detected by Western blotting. The expression of proliferating cell nuclear antigen (Ki67) was analyzed by immunohistochemistry. IAP level was detected by modified calcium cobalt staining and colorimetry. Immunofluorescence staining was used to detect the expression of Paneth cell marker molecule lysozyme 1 (LYZ1) and goblet cell marker molecule mucin 2 (MUC2). (2) Cell experiment: IEC6 cells in logarithmic growth stage were divided into blank control group and lipopolysaccharide (LPS) group (LPS 5 µg/mL). Twenty-four hours after treatment, PCR and Western blotting were used to analyze the transcription and translation of LGR5. The proliferation of IEC6 cells were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining. The transcription and translation of IAP were detected by PCR and colorimetric method respectively. RESULTS: (1) Animal experiment: the immunohistochemical results showed that the positive rate of Ki67 staining in the jejunal tissue of CLP group was lower than that of Sham group [(41.7±2.5)% vs. (48.7±1.4)%, P = 0.01]. PCR and Western blotting results showed that there were no statistical differences in the mRNA and protein expressions of LGR5 in the jejunal tissue between the CLP group and Sham group (Lgr5 mRNA: 0.7±0.1 vs. 1.0±0.2, P = 0.11; LGR5/ß-actin: 0.83±0.17 vs. 0.68±0.19, P = 0.24). The mRNA (0.4±0.1 vs. 1.0±0.1, P < 0.01) and protein (U/g: 47.3±6.0 vs. 73.1±15.3, P < 0.01) levels of IAP in the jejunal tissue were lower in CLP group. Immunofluorescence saining analysis showed that the expressions of LYZ1 and MUC2 in the CLP group were lower than those in the Sham group. (2) Cell experiment: PCR and Western blotting results showed that there was no significant difference in the expression of LGR5 between the LPS group and the blank control group (Lgr5 mRNA: 0.9±0.1 vs. 1.0±0.2, P = 0.33; LGR5/ß-actin: 0.71±0.18 vs. 0.69±0.04, P = 0.81). The proliferation rate of IEC6 cells in the LPS group was lower than that in the blank control group, but there was no significant difference [positivity rate of EdU: (40.5±3.8)% vs. (46.5±3.6)%, P = 0.11]. The mRNA (0.5±0.1 vs. 1.0±0.2, P < 0.01) and protein (U/g: 15.0±4.0 vs. 41.2±10.4, P < 0.01) of IAP in the LPS group were lower than those in the blank control group. CONCLUSIONS: CLP-induced sepsis inhibits the proliferation and differentiation of intestinal epithelial cells, impairing the self-renewal ability of intestinal epithelium.


Assuntos
Diferenciação Celular , Proliferação de Células , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas G , Sepse , Células-Tronco , Animais , Masculino , Sepse/metabolismo , Camundongos , Receptores Acoplados a Proteínas G/metabolismo , Células-Tronco/metabolismo , Células-Tronco/citologia , Ceco , Mucosa Intestinal/metabolismo , Ligadura , Mucina-2
8.
Acta Neuropathol ; 147(1): 95, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847845

RESUMO

The non-WNT/non-SHH (Grp3/Grp4) medulloblastomas (MBs) include eight second-generation subgroups (SGS; I-VIII) each with distinct molecular and clinical characteristics. Recently, we also identified two prognostically relevant transcriptome subtypes within each SGS MB, which are associated with unique gene expression signatures and signaling pathways. These prognostic subsets may be in connection to the intra-tumoral cell landscape that underlies SGS MB clinical-molecular diversity. Here, we performed a deconvolution analysis of the Grp3/Grp4 MB bulk RNA profiles using the previously identified single-cell RNA-seq reference dataset and focusing on variability in the cellular composition of SGS MB. RNA deconvolution analysis of the Grp3/Grp4 MB disclosed the subgroup-specific neoplastic cell subpopulations. Neuronally differentiated axodendritic GP3-C1 and glutamatergic GP4-C1 subpopulations were distributed within Grp3- and Grp4-associated SGS MB, respectively. Progenitor GP3-B2 subpopulation was prominent in aggressive SGS II MB, whereas photoreceptor/visual perception GP3/4-C2 cell content was typical for SGS III/IV MB. The current study also revealed significant variability in the proportions of cell subpopulations between clinically relevant SGS MB transcriptome subtypes, where unfavorable cohorts were enriched with cell cycle and progenitor-like cell subpopulations and, vice versa, favorable subtypes were composed of neuronally differentiated cell fractions predominantly. A higher than median proportion of proliferating and progenitor cell subpopulations conferred the shortest survival of the Grp3 and Grp 4 MB, and similar survival associations were identified for all SGS MB except SGS IV MB. In summary, the recently identified clinically relevant Grp3/Grp4 MB transcriptome subtypes are composed of different cell populations. Future studies should aim to validate the prognostic and therapeutic role of the identified Grp3/Grp4 MB inter-tumoral cellular heterogeneity. The application of the single-cell techniques on each SGS MB separately could help to clarify the clinical significance of subgroup-specific variability in tumor cell content and its relation with prognostic transcriptome signatures identified before.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Transcriptoma , Humanos , Meduloblastoma/genética , Meduloblastoma/patologia , Meduloblastoma/metabolismo , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/metabolismo , Proliferação de Células/genética , Masculino , Criança , Feminino , Pré-Escolar , Adolescente , Prognóstico
9.
Med Oncol ; 41(7): 170, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847902

RESUMO

Salvianolic acid B (Sal B) has demonstrated anticancer activity against various types of cancer. However, the underlying mechanism of Sal B-mediated anticancer effects remains incompletely understood. This study aims to investigate the impact of Sal B on the growth and metastasis of human A549 lung cells, as well as elucidate its potential mechanisms. In this study, different concentrations of Sal B were administered to A549 cells. The effects on migration and invasion abilities were assessed using MTT, wound healing, and transwell assays. Flow cytometry analysis was employed to evaluate Sal B-induced apoptosis in A549 cells. Western blotting and immunohistochemistry were conducted to measure the expression levels of cleaved caspase-3, cleaved PARP, and E-cadherin. Commercial kits were utilized for detecting intracellular reactive oxygen species (ROS) and NAD+. Additionally, a xenograft model with transplanted A549 tumors was employed to assess the anti-tumor effect of Sal B in vivo. The expression levels of NDRG2, p-PTEN, and p-AKT were determined through western blotting. Our findings demonstrate that Sal B effectively inhibits proliferation, migration, and invasion in A549 cells while inducing dose-dependent apoptosis. These apoptotic responses and inhibition of tumor cell metastasis are accompanied by alterations in intracellular ROS levels and NAD+/NADH ratio. Furthermore, our in vivo experiment reveals that Sal B significantly suppresses A549 tumor growth compared to an untreated control group while promoting increased cleavage of caspase-3 and PARP. Importantly, we observe that Sal B upregulates NDRG2 expression while downregulating p-PTEN and p-AKT expressions. Collectively, our results provide compelling evidence supporting the ability of Sal B to inhibit both growth and metastasis in A549 lung cancer cells through oxidative stress modulation as well as involvement of the NDRG2/PTEN/AKT pathway.


Assuntos
Benzofuranos , Movimento Celular , Proliferação de Células , Neoplasias Pulmonares , Estresse Oxidativo , PTEN Fosfo-Hidrolase , Transdução de Sinais , Humanos , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células A549 , Animais , Proliferação de Células/efeitos dos fármacos , Benzofuranos/farmacologia , Movimento Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Camundongos , Apoptose/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Depsídeos
10.
PeerJ ; 12: e17559, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854798

RESUMO

Background: To investigate the effects of arsenic trioxide (ATO) on human colorectal cancer cells (HCT116) growth and the role of transient receptor potential melastatin 4 (TRPM4) channel in this process. Methods: The viability of HCT116 cells was assessed using the CCK-8 assay. Western blot analysis was employed to examine the protein expression of TRPM4. The apoptosis of HCT116 cells was determined using TUNEL and Flow cytometry. Cell migration was assessed through the cell scratch recovery assay and Transwell cell migration assay. Additionally, Transwell cell invasion assay was performed to determine the invasion ability of HCT116 cells. Results: ATO suppressed the viability of HCT116 cells in a dose-dependent manner, accompanied by a decline in cell migration and invasion, and an increase in apoptosis. 9-phenanthroline (9-Ph), a specific inhibitor of TRPM4, abrogated the ATO-induced upregulation of TRPM4 expression. Additionally, blocking TRPM4 reversed the effects of ATO on HCT116 cells proliferation, including restoration of cell viability, migration and invasion, as well as the inhibition of apoptosis. Conclusion: ATO inhibits CRC cell growth by inducing TRPM4 expression, our findings indicate that ATO is a promising therapeutic strategy and TRPM4 may be a novel target for the treatment of CRC.


Assuntos
Apoptose , Trióxido de Arsênio , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Neoplasias Colorretais , Canais de Cátion TRPM , Humanos , Canais de Cátion TRPM/metabolismo , Canais de Cátion TRPM/antagonistas & inibidores , Canais de Cátion TRPM/genética , Trióxido de Arsênio/farmacologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Células HCT116 , Movimento Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Óxidos/farmacologia , Antineoplásicos/farmacologia , Invasividade Neoplásica , Arsenicais/farmacologia
11.
Front Immunol ; 15: 1369073, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855103

RESUMO

FAT1, a substantial transmembrane protein, plays a pivotal role in cellular adhesion and cell signaling. Numerous studies have documented frequent alterations in FAT1 across various cancer types, with its aberrant expression being linked to unfavorable survival rates and tumor progression. In the present investigation, we employed bioinformatic analyses, as well as in vitro and in vivo experiments to elucidate the functional significance of FAT1 in pan-cancer, with a primary focus on lung cancer. Our findings unveiled FAT1 overexpression in diverse cancer types, including lung cancer, concomitant with its association with an unfavorable prognosis. Furthermore, FAT1 is intricately involved in immune-related pathways and demonstrates a strong correlation with the expression of immune checkpoint genes. The suppression of FAT1 in lung cancer cells results in reduced cell proliferation, migration, and invasion. These collective findings suggest that FAT1 has potential utility both as a biomarker and as a therapeutic target for lung cancer.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/genética , Animais , Imunoterapia/métodos , Camundongos , Caderinas/metabolismo , Caderinas/genética , Linhagem Celular Tumoral , Prognóstico , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Movimento Celular , Biologia Computacional/métodos
12.
Theranostics ; 14(8): 3339-3357, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855186

RESUMO

Rationale: Skin cells actively metabolize nutrients to ensure cell proliferation and differentiation. Psoriasis is an immune-disorder-related skin disease with hyperproliferation in epidermal keratinocytes and is increasingly recognized to be associated with metabolic disturbance. However, the metabolic adaptations and underlying mechanisms of epidermal hyperproliferation in psoriatic skin remain largely unknown. Here, we explored the role of metabolic competition in epidermal cell proliferation and differentiation in psoriatic skin. Methods: Bulk- and single-cell RNA-sequencing, spatial transcriptomics, and glucose uptake experiments were used to analyze the metabolic differences in epidermal cells in psoriasis. Functional validation in vivo and in vitro was done using imiquimod-like mouse models and inflammatory organoid models. Results: We observed the highly proliferative basal cells in psoriasis act as the winners of the metabolic competition to uptake glucose from suprabasal cells. Using single-cell metabolic analysis, we found that the "winner cells" promote OXPHOS pathway upregulation by COX7B and lead to increased ROS through glucose metabolism, thereby promoting the hyperproliferation of basal cells in psoriasis. Also, to prevent toxic damage from ROS, basal cells activate the glutathione metabolic pathway to increase their antioxidant capacity to assist in psoriasis progression. We further found that COX7B promotes psoriasis development by modulating the activity of the PPAR signaling pathway by bulk RNA-seq analysis. We also observed glucose starvation and high expression of SLC7A11 that causes suprabasal cell disulfide stress and affects the actin cytoskeleton, leading to immature differentiation of suprabasal cells in psoriatic skin. Conclusion: Our study demonstrates the essential role of cellular metabolic competition for skin tissue homeostasis.


Assuntos
Diferenciação Celular , Proliferação de Células , Glucose , Queratinócitos , Psoríase , Psoríase/metabolismo , Psoríase/patologia , Glucose/metabolismo , Humanos , Animais , Camundongos , Queratinócitos/metabolismo , Modelos Animais de Doenças , Análise de Célula Única , Células Epidérmicas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Metabolismo Energético , Epiderme/metabolismo , Epiderme/patologia , Imiquimode , Masculino
13.
Int J Nanomedicine ; 19: 5125-5138, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855730

RESUMO

Purpose: Breast cancer is a prevalent malignancy among women worldwide, and malignancy is closely linked to the tumor microenvironment (TME). Here, we prepared mixed nano-sized formulations composed of pH-sensitive liposomes (Ber/Ru486@CLPs) and small-sized nano-micelles (Dox@CLGs). These liposomes and nano-micelles were modified by chondroitin sulfate (CS) to selectively target breast cancer cells. Methods: Ber/Ru486@CLPs and Dox@CLGs were prepared by thin-film dispersion and ethanol injection, respectively. To mimic actual TME, the in vitro "condition medium of fibroblasts + MCF-7" cell model and in vivo "4T1/NIH-3T3" co-implantation mice model were established to evaluate the anti-tumor effect of drugs. Results: The physicochemical properties showed that Dox@CLGs and Ber/Ru486@CLPs were 28 nm and 100 nm in particle size, respectively. In vitro experiments showed that the mixed formulations significantly improved drug uptake and inhibited cell proliferation and migration. The in vivo anti-tumor studies further confirmed the enhanced anti-tumor capabilities of Dox@CLGs + Ber/Ru486@CLPs, including smaller tumor volumes, weak collagen deposition, and low expression levels of α-SMA and CD31 proteins, leading to a superior anti-tumor effect. Conclusion: In brief, this combination therapy based on Dox@CLGs and Ber/Ru486@CLPs could effectively inhibit tumor development, which provides a promising approach for the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Proliferação de Células , Doxorrubicina , Lipossomos , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Animais , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Humanos , Camundongos , Lipossomos/química , Células MCF-7 , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacologia , Tamanho da Partícula , Sistemas de Liberação de Fármacos por Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Movimento Celular/efeitos dos fármacos , Nanopartículas/química
14.
Eur Rev Med Pharmacol Sci ; 28(10): 3473, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38856145

RESUMO

The Editor in Chief and the Publisher are issuing an expression of concern to alert readers to the fact that the following articles are under investigation due to concerns raised regarding non-verifiable nucleotide sequences and cell lines used in the following articles: -       Shi YX, Ye BL, Hu BR, Ruan XJ. Expression of miR-1294 is downregulated and predicts a poor prognosis in gastric cancer. Eur Rev Med Pharmacol Sci 2018; 22 (17): 5525-5530-DOI: 10.26355/eurrev_201809_15813-PMID: 30229824. -       Dong SR, Ju XL, Yang WZ. STAT5A reprograms fatty acid metabolism and promotes tumorigenesis of gastric cancer cells. Eur Rev Med Pharmacol Sci 2019; 23 (19): 8360-8370-DOI: 10.26355/eurrev_201910_19147-PMID: 31646566. -       Chen J, Yuan ZH, Hou XH, Shi MH, Jiang R. LINC01116 promotes the proliferation and inhibits the apoptosis of gastric cancer cells. Eur Rev Med Pharmacol Sci 2020; 24 (4): 1807-1814-DOI: 10.26355/eurrev_202002_20358-PMID: 32141549. Further updates will be provided once the investigation is completed. The authors have been notified about this expression of concern.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose , Proliferação de Células
15.
Carbohydr Polym ; 340: 122328, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38857995

RESUMO

This article presents a novel approach to treating prostate cancer using a nanocarrier composed of folic acid (FA), ß-cyclodextrin (ß-CD), and magnetic graphene oxide (MGO) as a theranostic agent. The carrier is designed to improve the solubility and bioavailability of curcumin, a potential therapeutic substance against prostate cancer. Folic acid receptors overexpressed on the surface of solid tumors, including prostate cancer, may facilitate targeted drug delivery to tumor cells while avoiding nonspecific effects on healthy tissues. The anticancer efficacy of Folic acid-curcumin@ß-CD-MGO in vitro was also examined on LNCaP (an androgen-dependent) and PC3 (an androgen-independent) prostate cancer cells. The relaxivity of nanoparticles in MRI images was also investigated as a diagnostic factor. The results showed a concentration-dependent inhibitory effect on cell proliferation, induction of oxidative damage, and apoptotic effects. Also, nanoparticle relaxometry shows that this agent can be used as a negative contrast agent in MRI images. Overall, this study represents a promising theranostic agent to improve the delivery and trace of curcumin and enhance its therapeutic potential in the treatment of prostate cancer.


Assuntos
Proliferação de Células , Curcumina , Ácido Fólico , Grafite , Neoplasias da Próstata , Nanomedicina Teranóstica , beta-Ciclodextrinas , Curcumina/química , Curcumina/farmacologia , Masculino , Grafite/química , Grafite/farmacologia , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , beta-Ciclodextrinas/química , Nanomedicina Teranóstica/métodos , Ácido Fólico/química , Ácido Fólico/farmacologia , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Portadores de Fármacos/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Receptores de Folato com Âncoras de GPI/metabolismo , Liberação Controlada de Fármacos , Nanopartículas de Magnetita/química
16.
Chem Biol Drug Des ; 103(6): e14567, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38858165

RESUMO

BACKGROUND: To explore the anti-tumor and anti-virus key active ingredients of Sini Decoction Plus Ginseng Soup (SNRS) and their mechanisms. METHODS: The main ingredients of SNRS were analyzed by network pharmacology, and quercetin was identified as the key active ingredient. Then, we obtained the targets of quercetin by using Drugbank, PharmMapper, and SwissTargetPrediction databases. Then, the targets of HBV-related hepatocellular carcinoma (HBV-related HCC) were obtained by using Genecards database. In addition, using the gene expression profiles of HBV-related HCC patients in GEO database and the genes with the greatest survival difference in GEPIA 2 database identified the potential targets of quercetin. In addition, the mechanism of potential genes was studied through GO, KEGG analysis, and PPI network. Using AUC and survival analysis to evaluate the diagnostic and prognostic value of cyclin-dependent kinase 1 (CDK1) and CCNB1. Finally, the effects of quercetin on proliferation of Hep3B and HepG2215 cells and the level of CDK1 and CCNB1 were verified in vitro. ELISA was used to measure the expression levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) after the intervention by quercetin for 24 h and 48 h in HepG2215 cell. RESULTS: The first 10 key ingredients of SNRS were identified, and quercetin was the most key ingredient. The 101 potential quercetin targets were identified for the treatment of HBV-related HCC. GO and KEGG showed that 101 potential target enrichment in cancer and cell cycle regulation. By Venn analysis, CDK1 and CCNB1 were intersection targets, which could be used as potential targets for the action of quercetin on HBV-related HCC. Moreover, the expression of CDK1 and CCNB1 was highly expressed in the high-risk group, while the OS rate was low. The 1-year, 3-year and 5-year area under the curve (AUC) curves of CDK1 and CCNB1 were 0.724, 0.676, 0.622 and 0.745, 0.678, 0.634, respectively. Moreover, experimental results also showed that quercetin inhibited cell proliferation and reduced CDK1 expression in Hep3B and HepG2215 cells. The expressions of HBsAg and HBeAg in HepG2215 cell supernatant and cell gradually decreased with the increase of intervention time of quercetin and CDK1 inhibitor. CONCLUSIONS: Quercetin is a key ingredient of anti-HBV-related HCC activity and inhibits HBV replication in SNRS by inhibiting CDK1.


Assuntos
Proteína Quinase CDC2 , Ciclina B1 , Vírus da Hepatite B , Neoplasias Hepáticas , Panax , Quercetina , Replicação Viral , Quercetina/farmacologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virologia , Vírus da Hepatite B/efeitos dos fármacos , Proteína Quinase CDC2/metabolismo , Panax/química , Replicação Viral/efeitos dos fármacos , Ciclina B1/metabolismo , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Antivirais/farmacologia , Antivirais/química , Células Hep G2
17.
FASEB J ; 38(12): e23735, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38860936

RESUMO

Identification of potential key targets of melanoma, a fatal skin malignancy, is critical to the development of new cancer therapies. Lysine methyltransferase 2A (KMT2A) promotes melanoma growth by activating the human telomerase reverse transcriptase (hTERT) signaling pathway; however, the exact mechanism remains elusive. This study aimed to reveal new molecular targets that regulate KMT2A expression and melanoma growth. Using biotin-streptavidin-agarose pull-down and proteomics, we identified Damage-specific DNA-binding protein 2 (DDB2) as a KMT2A promoter-binding protein in melanoma cells and validated its role as a regulator of KMT2A/hTERT signaling. DDB2 knockdown inhibited the expression of KMT2A and hTERT and inhibited the growth of melanoma cells in vitro. Conversely, overexpression of DDB2 activated the expression of KMT2A and promoted the growth of melanoma cells. Additionally, we demonstrated that DDB2 expression was higher in tumor tissues of patients with melanoma than in corresponding normal tissues and was positively correlated with KMT2A expression. Kaplan-Meier analysis showed a poor prognosis in patients with high levels of DDB2 and KMT2A. Overall, our data suggest that DDB2 promotes melanoma cell growth through the transcriptional regulation of KMT2A expression and predicts poor prognosis. Therefore, targeting DDB2 may regulate the effects of KMT2A on melanoma growth and progression, providing a new potential therapeutic strategy for melanoma.


Assuntos
Proliferação de Células , Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica , Histona-Lisina N-Metiltransferase , Melanoma , Proteína de Leucina Linfoide-Mieloide , Humanos , Melanoma/genética , Melanoma/patologia , Melanoma/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Prognóstico , Linhagem Celular Tumoral , Feminino , Masculino , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo
18.
Mol Biol Rep ; 51(1): 728, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861185

RESUMO

INTRODUCTION: Colorectal cancer (CRC) is the second common cancer and the fourth major reason of cancer death worldwide. Dysregulation of intracellular pathways, such as TGF-ß/SMAD signaling, contributes to CRC development. MicroRNAs (miRNAs) are post-transcriptional regulators that are involved in CRC pathogenesis. Here, we aimed to investigate the effect of miR-3613-3p on the TGF-ß /SMAD signaling pathway in CRC. METHODS & RESULTS: Bioinformatics analysis suggested that miR-3613-3p is a regulator of TGF-Β signaling downstream genes. Then, miR-3613-3p overexpression was followed by downregulation of TGF-ßR1, TGF-ßR2, and SMAD2 expression levels, detected by RT-qPCR. Additionally, dual luciferase assay supported the direct interaction of miR-3613-3p with 3'UTR sequences of TGF-ßR1 and TGF-ßR2 genes. Furthermore, reduced SMAD3 protein level following the miR-3613-3p overexpression verified its suppressive effect against TGF-ß signaling in HCT-116 cells, detected by western blot analysis. Finally, miR-3613-3p overexpression induced sub-G1 arrest in HCT116 cells, detected by flow cytometry, and promoted downregulation of cyclin D1 protein expression, which was detected by western blotting analysis. CONCLUSION: Our findings indicated that miR-3613-3p plays an important role in CRC by targeting the TGF-ß/SMAD signaling pathway and could be considered as a new candidate for further therapy investigations.


Assuntos
Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Transdução de Sinais , Fator de Crescimento Transformador beta , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/genética , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Proteína Smad2/metabolismo , Proteína Smad2/genética , Proliferação de Células/genética , Regiões 3' não Traduzidas/genética , Linhagem Celular Tumoral , Proteína Smad3/genética , Proteína Smad3/metabolismo
19.
PLoS One ; 19(6): e0304149, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38848430

RESUMO

Glioblastoma, the most aggressive form of brain cancer, poses a significant global health challenge with a considerable mortality rate. With the predicted increase in glioblastoma incidence, there is an urgent need for more effective treatment strategies. In this study, we explore the potential of caerin 1.1 and 1.9, host defence peptides derived from an Australian tree frog, in inhibiting glioblastoma U87 and U118 cell growth. Our findings demonstrate the inhibitory impact of caerin 1.1 and 1.9 on cell growth through CCK8 assays. Additionally, these peptides effectively curtail the migration of glioblastoma cells in a cell scratch assay, exhibiting varying inhibitory effects among different cell lines. Notably, the peptides hinder the G0/S phase replication in both U87 and U118 cells, pointing to their impact on the cell cycle. Furthermore, caerin 1.1 and 1.9 show the ability to enter the cytoplasm of glioblastoma cells, influencing the morphology of mitochondria. Proteomics experiments reveal intriguing insights, with a decrease in CHI3L1 expression and an increase in PZP and JUNB expression after peptide treatment. These proteins play roles in cell energy metabolism and inflammatory response, suggesting a multifaceted impact on glioblastoma cells. In conclusion, our study underscores the substantial anticancer potential of caerin 1.1 and 1.9 against glioblastoma cells. These findings propose the peptides as promising candidates for further exploration in the realm of glioblastoma management, offering new avenues for developing effective treatment strategies.


Assuntos
Proliferação de Células , Regulação para Baixo , Glioblastoma , Mitocôndrias , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Proliferação de Células/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Respiração Celular/efeitos dos fármacos , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Movimento Celular/efeitos dos fármacos
20.
BMC Pregnancy Childbirth ; 24(1): 414, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849756

RESUMO

CircRNAs are a class of endogenous non-coding RNAs implicated in the pathogenesis of many pregnancy related diseases, one of which is pre-eclampsia (PE). This study aims to investigate the role of CircPAPPA2 (circbase ID: hsa_circ_0015382) in regulating the migration and invasion of trophoblast cells. RNA sequencing was used to identify the differentially expressed circRNAs in placenta of PE and normal pregnant women. Quantitative polymerase chain reaction (qRT-PCR) was used to verify the expression of circPAPPA2 and two miRNAs (miR-942-5p, 5006-3p) in placenta of PE and normal pregnant women. CCK8 and transwell experiments were performed to assess the function of circPAPPA2 in PE development.The interaction between circPAPPA2 and miR-942-5p/miR-5006-3p was verified by dual-luciferase reporter assay. Finally, bioinformatics analyzed with gene ontology, Kyoto Encyclopedia of the target genes. The results showed that the expression of circPAPPA2 was increased in placenta of PE pregnant women. Also, circPAPPA2 impedes trophoblasts cell proliferation and invasion. Moreover, the expression of circPAPPA2 was positively correlated with systolic blood pressure and urine protein. In addition, circPAPPA2 serves as a sponge of miR-942-5p and miR-5006-3p. In conclusion, CircPAPPA2 regulates trophoblasts cell proliferation and invasion by mediating the miR-942/miR-5006-3p.


Assuntos
MicroRNAs , Placenta , Pré-Eclâmpsia , RNA Circular , Trofoblastos , Humanos , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Gravidez , RNA Circular/genética , Trofoblastos/metabolismo , Placenta/metabolismo , Adulto , Movimento Celular/genética , Proliferação de Células/genética , Estudos de Casos e Controles
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