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BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive malignant tumor with poor prognosis. Using high-throughput sequencing, we identified a novel circRNA, circGNAO1, which is downregulated in HCC tissues compared to adjacent tissues. However, the potential functions and mechanisms of circGNAO1 in HCC metastasis remain unclear. METHODS: qRT-PCR was used to detect the expression of circGNAO1, miR-182-5p, and FOXO1 in HCC cells and tissues. Bioinformatics analysis, RNA pull-down assyas, and dual-luciferase reporter assays were employed to verify the interaction between circGNAO1 and miR-182-5p. Functional experiments were conducted using circGNAO1 overexpression and knockdown cell lines, including Transwell, wound healing, and EdU assays. Liver metastasis models and subcutaneous xenograft mouse models were established to analyze the effect of circGNAO1 on HCC metastasis and growth in vivo. RESULTS: High-throughput sequencing and qRT-PCR results showed that the expression of circGNAO1 dramatically decreased in HCC tissues. Functionally, in vivo and in vitro experiments verified that overexpression of circGNAO1 inhibited the proliferation, migration, invasion and EMT of HCC cells, while knockdown of circGNAO1 promoted these behaviors. Mechanistically, we have demonstrated that circGNAO1 functions as a sponge for miR-182-5p to regulate FOXO1 expression, thereby activating the TGF-ß/Smad3 signaling pathway and EMT process. CONCLUSIONS: circGNAO1 suppresses the progression and metastasis of HCC through the miR-182-5p/FOXO1 axis, and circGNAO1 may be an efficient therapeutic target in HCC.
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Oral squamous cell carcinoma (OSCC), a major subtype of head and neck cancers, presents significant challenges due to its aggressive feature and limited therapeutic efficacy of conventional treatments. In response to these challenges, Natural Killer (NK) cells, a vital component of the innate immune system, are being explored for their therapeutic potential in OSCC due to their inherent ability to target and eliminate cancer cells without prior sensitization. This review uniquely focuses on the evolving role of NK cells specifically in OSCC, incorporating recent advancements in CAR-NK cell engineering and personalized therapy approaches that have not been comprehensively covered in previous reviews. The mechanisms through which NK cells exert cytotoxic effects on tumor cells include direct killing through the engagement of natural cytotoxic receptors and antibody-dependent cellular cytotoxicity (ADCC), making them promising agents in cancer immunotherapy. Additionally, the article explores recent advancements in engineering NK cells to enhance their antitumor activity, such as the modification with chimeric antigen receptors (CARs) to target specific tumor antigens. Clinical implications of NK cell-based therapies, including the challenges of integrating these treatments with existing protocols and the potential for personalized therapy, are examined. The review highlights the promise of NK cell therapies in improving outcomes for OSCC patients and outlines future directions for research in this dynamic field of oncological immunotherapy.
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Células Asesinas Naturales , Neoplasias de la Boca , Humanos , Células Asesinas Naturales/inmunología , Neoplasias de la Boca/terapia , Neoplasias de la Boca/inmunología , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Animales , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/inmunología , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Inmunoterapia/métodosRESUMEN
Low-dose 5-aminolevulinic acid photodynamic therapy (ALA-PDT) has been used to cope with skin photoaging, and is thought to involve DNA damage repair responses. However, it is still unknown how low-dose ALA-PDT regulates DNA damage repair to curb skin photoaging. We established a photoaging model using human dermal fibroblasts (HDFs) and rat skin. RNA-sequencing (RNA-seq) analysis was conducted to identify differentially expressed genes (DEGs) in HDFs before and after low-dose ALA-PDT treatment, followed by bioinformatics analysis. Senescence-associated ß-galactosidase (SA-ß-gal) staining was employed to assess skin aging-related manifestations and Western blotting to evaluate the expression of associated proteins. A comet assay was used to detect cellular DNA damage, while immunofluorescence to examine the expression of 8-hydroxy-2'-deoxyguanosine (8-oxo-dG) in cells and skin tissues. In both in vivo and in vitro models, low-dose ALA-PDT alleviated the manifestations of ultraviolet B (UVB)-induced skin photoaging. Low-dose ALA-PDT significantly reduced DNA damage in photoaged HDFs. Furthermore, low-dose ALA-PDT accelerated the clearance of the photoproduct 8-oxo-dG in photoaged HDFs and superficial dermis of photoaged rat skin. RNA-seq analysis suggested that low-dose ALA-PDT upregulated the expression of key genes in the base excision repair (BER) pathway. Further functional validation showed that inhibition on BER expression by using UPF1069 significantly suppressed SA-ß-gal activity, G2/M phase ratio, expression of aging-associated proteins P16, P21, P53, and MUTYH proteins, as well as clearance of the photoproduct 8-oxo-dG in photoaged HDFs. Low-dose ALA-PDT exerts anti-photoaging effects by activating the BER signalling pathway.
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Ácido Aminolevulínico , Daño del ADN , Reparación del ADN , Fibroblastos , Fotoquimioterapia , Transducción de Señal , Envejecimiento de la Piel , Rayos Ultravioleta , Ácido Aminolevulínico/farmacología , Reparación del ADN/efectos de los fármacos , Animales , Rayos Ultravioleta/efectos adversos , Humanos , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Transducción de Señal/efectos de los fármacos , Fotoquimioterapia/métodos , Ratas , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/efectos de la radiación , Daño del ADN/efectos de los fármacos , Piel/efectos de los fármacos , Piel/metabolismo , Piel/efectos de la radiación , Piel/patología , Masculino , Fármacos Fotosensibilizantes/farmacología , 8-Hidroxi-2'-Desoxicoguanosina/metabolismoRESUMEN
CircRNAs are a class of highly stable noncoding RNAs that play an important role in the progression of many diseases, especially cancer. In this study, high-throughput sequencing was used to screen for abnormally expressed circRNAs, and we found that circGPC3 was overexpressed in HCC tissues. However, the underlying mechanism of circGPC3 in the development and metastasis of hepatocellular carcinoma (HCC) remains unknown. In our study, we found that circGPC3 was significantly upregulated in HCC tissues and cells and that its overexpression was positively correlated with overall survival, TNM stage and lymph node metastasis. In vivo and in vitro experiments showed that circGPC3 knockdown repressed HCC cell migration, invasion and proliferation and promoted apoptosis. Mechanistically, circGPC3 promoted HCC proliferation and metastasis through the miR-578/RAB7A/PSME3 axis. Our results demonstrate that circGPC3 contributes to the progression of HCC and provides an intervention target for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , ARN Largo no Codificante/metabolismoRESUMEN
Circular RNA (circRNA) can influence the development of hepatocellular carcinoma (HCC) as a competitive endogenous RNA (ceRNA). However, there are still many circRNAs whose functions are unknown. Our research explores the role of a novel circRNA, hsa_circ_0079875, in HCC. The expression of hsa_circ_0079875 in HCC was verified by next-generation sequencing, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and fluorescence in situ hybridization (FISH). The distribution of hsa_circ_0079875 in HCC cells was investigated by RNA subcellular isolation and FISH assays. The functional effects on HCC proliferation, invasion, migration, cell cycle, and apoptosis were verified by overexpression and knockdown of hsa_circ_0079875. Moreover, xenograft mouse models and immunohistochemistry experiments were used to assess the function of hsa_circ_0079875 in vivo. Hsa_circ_0079875 was up-regulated in HCC tissues and mainly distributed in the cytoplasm. Higher hsa_circ_0079875 leads to larger tumor tissue, more microvascular invasion(MVI) and higher AFP levels, which in turn leads to a poor prognosis. Overexpression of hsa_circ_0079875 can promote the proliferation, migration, and invasion of HCC cells and inhibit apoptosis in vitro and in vivo. Knocking down hsa_circ_0079875 has the opposite effect. Sequencing and biological information predicted the target miRNA and mRNA of hsa_circ_0079875. Further bioinformatics and clinical correlation analysis revealed that hsa_circ_0079875 promote the malignant biological behaviors of HCC through hsa_circ_0079875/miR-519d-59/NRAS ceRNA net. Therefore, hsa_circ_0079875 can be a potential prognostic marker and therapeutic target for HCC.
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Apoptosis , Carcinoma Hepatocelular , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Neoplasias Hepáticas , Ratones Desnudos , ARN Circular , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Animales , Proliferación Celular/genética , Movimiento Celular/genética , Apoptosis/genética , Masculino , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Ratones , Persona de Mediana Edad , Ratones Endogámicos BALB C , Invasividad Neoplásica/genética , ARN/metabolismo , ARN/genética , MicroARNs/genética , MicroARNs/metabolismo , ARN Endógeno CompetitivoRESUMEN
Diesel exhaust particles (DEPs) are major air pollutants emitted from automobile engines. Prenatal exposure to DEPs has been linked to neurodevelopmental and neurodegenerative diseases associated with aging. However, the specific mechanism by DEPs impair the hippocampal synaptic plasticity in the offspring remains unclear. Pregnant C57BL/6 mice were administered DEPs solution via the tail vein every other day for a total of 10 injections, then the male offsprings were studied to assess learning and memory by the Morris water maze. Additionally, protein expression in the hippocampus, including CPEB3, NMDAR (NR1, NR2A, NR2B), PKA, SYP, PSD95, and p-CREB was analyzed using Western blotting and immunohistochemistry. The alterations in the histomorphology of the hippocampus were observed in male offspring on postnatal day 7 following prenatal exposure to DEPs. Furthermore, 8-week-old male offspring exposed to DEPs during prenatal development exhibited impairments in the Morris water maze test, indicating deficits in learning and memory. Mechanistically, the findings from our study indicate that exposure to DEPs during pregnancy may alter the expression of CPEB3, SYP, PSD95, NMDAR (NR1, NR2A, and NR2B), PKA, and p-CREB in the hippocampus of both immature and mature male offspring. The results offer evidence for the role of the NMDAR/PKA/CREB and CPEB3 signaling pathway in mediating the learning and memory toxicity of DEPs in male offspring mice. The alterations in signaling pathways may contribute to the observed damage to synaptic structure and transmission function plasticity caused by DEPs. The findings hold potential for informing future safety assessments of DEPs.
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Efectos Tardíos de la Exposición Prenatal , Emisiones de Vehículos , Femenino , Embarazo , Humanos , Ratones , Animales , Masculino , Emisiones de Vehículos/toxicidad , Aprendizaje por Laberinto , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratones Endogámicos C57BL , Receptores de N-Metil-D-Aspartato/metabolismo , Hipocampo/metabolismo , Plasticidad Neuronal , Proteínas de Unión al ARN/metabolismoRESUMEN
Keratinocytes, located in the outermost layer of human skin, are pivotal cells to resist environmental damage. Cellular autophagy plays a critical role in eliminating damaged organelles and maintaining skin cell homeostasis. Low-dose 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been demonstrated to enhance skin's antistress ability; however, the regulatory mechanisms of autophagy in keratinocytes remain unclear. In this study, we treated immortalized human keratinocytes (HaCaT cells) with low-dose ALA-PDT (0.5 mmol/L, 3 J/cm2). Through RNA-sequencing analysis, we identified that low-dose ALA-PDT modulated autophagy-related pathways in keratinocytes and pinpointed Unc-51-like kinase 1 (ULK1) as a key gene involved. Western blot results revealed that low-dose ALA-PDT treatment upregulated the expression of autophagy-related proteins Beclin-1 and LC3-II/LC3-I ratio. Notably, low-dose ALA-PDT regulated autophagy by inducing an appropriate level of reactive oxygen species (ROS), transiently reducing mitochondrial membrane potential, and decreasing adenosine triphosphate production; all these processes functioned on the AMP-activated protein kinase (AMPK)/ULK1 pathway to activate autophagy. Finally, we simulated external environmental damage using ultraviolet B (UVB) at a dose of 60 mJ/cm2 and observed that low-dose ALA-PDT mitigated UVB-induced cell apoptosis; however, this protective effect was reversed when using the autophagy inhibitor 3-methyladenine. Overall, these findings highlight how low-dose ALA-PDT enhances antistress ability in HaCaT cells through controlling ROS generation and activating the AMPK/ULK1 pathway to arouse cellular autophagy.
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Proteínas Quinasas Activadas por AMP , Homólogo de la Proteína 1 Relacionada con la Autofagia , Autofagia , Queratinocitos , Transducción de Señal , Humanos , Ácido Aminolevulínico/farmacología , Proteínas Quinasas Activadas por AMP/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia/efectos de los fármacos , Homólogo de la Proteína 1 Relacionada con la Autofagia/efectos de los fármacos , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Células HaCaT , Queratinocitos/metabolismo , Queratinocitos/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , FotoquimioterapiaRESUMEN
PURPOSE: The purpose of this study was to explore the expression and potential mechanism of hsa_circ_0005397 in hepatocellular carcinoma progression. METHODS: Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) was used to measure the expression level of hsa_circ_0005397 and EIF4A3 from paired HCC tissues and cell lines. Western Blot (WB) and immunohistochemistry (IHC) were used to verify the protein level of EIF4A3. The specificity of primers was confirmed by agarose gel electrophoresis. Receiver Operating Characteristic (ROC) Curve was drawn to analyze diagnostic value. Actinomycin D and nuclear and cytoplasmic extraction assays were utilized to evaluate the characteristics of hsa_circ_0005397. Cell Counting kit-8 (CCK-8) and colony formation assays were performed to detect cell proliferation. Flow cytometry analysis was used to detect the cell cycle. Transwell assay was performed to determine migration and invasion ability. RNA-binding proteins (RBPs) of hsa_circ_0005397 in HCC were explored using bioinformatics websites. The relationship between hsa_circ_0005397 and Eukaryotic Translation Initiation Factor 4A3 (EIF4A3) was verified by RNA Binding Protein Immunoprecipitation (RIP) assays, correlation and rescue experiments. RESULTS: In this study, hsa_circ_0005397 was found to be significantly upregulated in HCC, and the good diagnostic sensitivity and specificity shown a potential diagnostic capability. Upregulated expression of hsa_circ_0005397 was significantly related to tumor size and stage. Hsa_circ_0005397 was circular structure which more stable than liner mRNA, and mostly distributed in the cytoplasm. Upregulation of hsa_circ_0005397 generally resulted in stronger proliferative ability, clonality, and metastatic potency of HCC cells; its downregulation yielded the opposite results. EIF4A3 is an RNA-binding protein of hsa_circ_0005397, which overexpressed in paired HCC tissues and cell lines. In addition, expression of hsa_circ_0005397 decreased equally when EIF4A3 was depleted. RIP assays and correlation assay estimated that EIF4A3 could interacted with hsa_circ_0005397. Knockdown of EIF4A3 could reverse hsa_circ_0005397 function in HCC progression. CONCLUSIONS: Hsa_circ_0005397 promotes progression of hepatocellular carcinoma through EIF4A3. These research findings may provide novel clinical value for hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , ARN Circular/genética , ARN Circular/metabolismo , Regulación hacia Abajo , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Factor 4A Eucariótico de Iniciación/genética , Factor 4A Eucariótico de Iniciación/metabolismo , ARN Helicasas DEAD-box/genéticaRESUMEN
Worldwide, primary liver cancer is the third leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Recent studies have shown that circular RNAs (circRNAs) that interact with microRNAs (miRNAs) are involved in the occurrence and development of various tumours. Transcriptional profile analysis was used to analyse expression of circRNAs in HCC in this study. The top ten upregulated circRNAs were selected and validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in another 34 HCC patients. MiRNAs and mRNAs downstream of these circRNAs were explored through database analysis, and finally, the competitive endogenous RNA (ceRNA) networks were constructed for 5 selected circRNAs. We identified 9658 differentially expressed circRNAs by transcriptional profile analysis. QRT-PCR was performed to validate the top ten upregulated circRNAs, and five circRNAs were selected for further analysis. The miRNAs and mRNAs downstream of these five circRNAs were predicted to construct ceRNA network diagrams. Further analysis revealed five circRNA-miRNA-mRNA axes that correlate negatively with HCC prognosis. Numerous differentially expressed circRNAs exist in HCC, and they can regulate the biological behaviour of HCC through ceRNA networks. Bioinformatics analysis showed that ceRNA regulatory axes involved in HCC have high diagnostic and prognostic value and deserve further exploration.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , ARN Endógeno Competitivo , ARN Circular/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Redes Reguladoras de Genes , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Liver cancer resection, especially in patients with hemihepatectomy or extended hemihepatectomy, often leads to poor prognosis, such as liver insufficiency and even liver failure and death, because the standard residual liver volume (SRLV) cannot be fully compensated after surgery. AIM: To explore the risk factors of poor prognosis after hemihepatectomy for hepatocellular carcinoma and evaluate the application value of related prognostic approaches. METHODS: The clinical data of 35 patients with primary liver cancer in Nantong Third People's Hospital from February 2016 to July 2020 were retrospectively analyzed. The receiver operating characteristic curve was created using medcac19.0.4 to compare the critical values of the SRLV in different stages of liver fibrosis after hemihepatectomy with those of liver dysfunction after hemihepatectomy. It was constructed by combining the Child-Pugh score to evaluate its application value in predicting liver function compensation. RESULTS: The liver stiffness measure (LSM) value and SRLV were associated with liver dysfunction after hemihepatectomy. Logistic regression analysis showed that an LSM value ≥ 25 kPa [odds ratio (OR) = 6.254, P < 0.05] and SRLV ≤ 0.290 L/m2 (OR = 5.686, P < 0.05) were independent risk factors for postoperative liver dysfunction. The accuracy of the new liver reserve evaluation model for predicting postoperative liver function was higher than that of the Child-Pugh score (P < 0.05). CONCLUSION: SRLV and LSM values can be used to evaluate the safety of hemihepatectomy. The new liver reserve evaluation model has good application potential in the evaluation of liver reserve function after hemihepatectomy.
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Circular RNAs (circRNAs) are noncoding RNAs with a circular colsed structure that play an important role in the occurrence and development of cancers. The functional mechanism of circRNAs as ceRNAs in hepatocellular carcinoma (HCC) and its effect on the invasion and metastasis of HCC need to be further studied. Five pairs of HCC tissues were selected for high-throughput sequencing, and 19 circRNAs with differential expression were obtained. The expression of circSLCO1B7 was obviously downregulated in 50 pairs of tumor tissues and plasma of HCC patients, which was closely related to the TNM stage, lymph node metastasis and tumor size. Cell functional experiments showed that circSLCO1B7 could inhibit cell growth, migration, invasion and promote cell apoptosis. In the regulatory mechanism, circSLCO1B7 sponged miR-556-3p to regulate the expression of the downstream target gene DAB2IP and induced the Epithelial-mesenchymal transition (EMT) progression. Our results indicated that circSLCO1B7 significantly inhibits the metastasis of HCC via the miR-556-3p/DAB2IP axis. Thus, circSLCO1B7 is a good candidate as a therapeutic target.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Activadoras de ras GTPasa/metabolismo , ARN Circular/genéticaRESUMEN
Cuproptosis is a new mechanism of cell death that differs from previously identified regulatory cell death mechanisms. Cuproptosis induction holds promise as a new tumour treatment. Therefore, we investigated the value of cuproptosis-related genes in the management of hepatocellular carcinoma (HCC). The cuproptosis-related gene Dihydrolipoamide S-Acetyltransferase (DLAT) were significantly upregulated in liver cancer tissues. High levels of DLAT were an independent prognostic factor for shorter overallsurvival (OS) time. DLAT and its related genes were mainly involved in cell metabolism, tumor progression and immune regulation. DLAT was significantly associated with the level of immune cell infiltration and immune checkpoints in HCC. HCC with high DLAT expression was predicted to be more sensitive to sorafenib treatment. The risk prognostic signature established based on DLAT and its related genes had a good prognostic value. The cuproptosis-related gene DLAT is a promising independent prognostic marker and therapeutic target in HCC. The new prognostic signature can effectively predict the prognosis of HCC patients.
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Carcinoma Hepatocelular , Acetiltransferasa de Residuos Dihidrolipoil-Lisina , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Pronóstico , Sorafenib/uso terapéuticoRESUMEN
BACKGROUND: Semaphorin4F (Sema4F) is a member of the semaphorin family and exhibits important regulatory functions in cancer biology. We aimed to explore the prognostic value and biologic function of Sema4F in gastric cancer (GC) through clinical data, laboratory studies, and bioinformatic methods. METHODS: We investigated Sema4F-related data and the prognostic values of patients with GC based on several databases, including Tumor Immune Estimation Resource (TIMER), the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), The University Of Alabama At Birmingham Cancer Data Analysis Portal (UALCAN) and Kaplan-Meier Plotter. We detected the expression of Sema4F in cell lines and tumor tissues by reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry. The prognostic value of Sema4F expression on patient overall survival was analyzed retrospectively using Kaplan-Meier survival and Cox regression analyses. Moreover, we used Kyoto encyclopedia of genes and genomes (KEGG), Gene Ontology (GO) and Gene-set enrichment analysis (GSEA) analyses to explore the relevant pathways of Sema4F in GC. RESULTS: The expression of Sema4F was markedly increased in cancer tissues and cancer cell lines. Furthermore, high Sema4F expression was positively associated with various clinicopathologic data and independently predicted poor prognosis for overall survival in GC. Our functional enrichment analysis revealed that Sema4F was mainly involved in oxidative phosphorylation and tumor-related signaling pathways. CONCLUSIONS: Sema4F may be a valuable prognostic biomarker and a novel target for gastric cancer.
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Background: Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Worldwide, liver cancer is the fourth most common cause of cancer-related death. Recent studies have found that PIWI-interacting RNAs (piRNAs) participate in the occurrence and development of various tumors and are closely related to the growth, invasion, metastasis and prognosis of malignant tumors. Studies on the role and functional mechanism of piRNAs in HCC development and progression are limited. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expression of piR-017724 in both HCC tissues and cells. Based on the clinical data of HCC patients, the clinical and prognostic value of piR-017724 was further analyzed. Then, targeted silencing and overexpressing of piR-017724 in HCC cells was further used to examine the biological functions of piR-017724. In addition, the downstream target protein of piR-017724 was predicted and validated through high-throughput sequencing and public databases. Results: The piR-017724 was significantly downregulated in HCC tissues and cells, and the downregulation of piR-017724 was associated with tumor stage and poor prognosis in HCC. The piR-017724 inhibitor promoted the proliferation, migration and invasion of HCC cells, while the piR-017724 mimic had the opposite effect. However, the piR-017724 did not affect apoptosis of HCC cells. High-throughput sequencing and qRT-PCR confirmed a reciprocal relationship between piR-017724 and PLIN3. Therefore, we speculate that piR-017724 may inhibit the development and progression of HCC by affecting the downstream protein PLIN3. Conclusions: Our study shows that piR-017724, which is lowly expressed in HCC, inhibits the proliferation, migration and invasion of HCC cells and may affect the development of hepatocellular liver cancer through PLIN3, which provides new insights into the clinical application of piR-017724 in the treatment of hepatocellular carcinoma.
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Mucosal-associated invariant T (MAIT) cells are important in antibacterial immune responses; however, during sepsis, they are few in number and exhibit highly activated phenotypes. The relationship between MAIT cells in peripheral blood and the prognosis of sepsis is not well understood. Thus, this study aimed to examine the levels and phenotypes of MAIT cells in early sepsis, evaluate their clinical relevance, and investigate their association with patient prognosis. This prospective observational study enrolled 72 septic patients defined according to the Sepsis 3.0 criteria and 21 healthy controls matched for age and sex. Their peripheral blood samples were used to assay the expression of immune activation (CD69 and HLA-DR) and immune checkpoint (PD-1 and PD-L1) markers on MAIT cells. The systemic inflammatory response syndrome, acute physiology and chronic health evaluation (APACHE) II, and sequential organ failure assessment scores were recorded. Subsequently, the association between MAIT cell characteristics and clinical indicators was assessed using Spearman's rank correlation analysis, and binary logistic regression analysis with a forward stepwise approach assessed independent risk factors for 28-day mortality. We noted a decrease in the percentage of MAIT cells in the patients' peripheral blood, which exhibited an activated phenotype. Besides, HLA-DR+ MAIT cell percentage and the APACHE II score were independently associated with the 28-day mortality and, in combination, were the best indicators of mortality. Thus, the percentage of HLA-DR+ MAIT cells in early sepsis serves as a novel prognostic biomarker for predicting mortality and improves the predictive capacity of the APACHE II score.
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Células T Invariantes Asociadas a Mucosa , Sepsis , Humanos , Antígenos HLA-DR , Sepsis/diagnóstico , Pronóstico , Estudios ProspectivosRESUMEN
INTRODUCTION: The aim of this study was to investigate the relationship between the high mobility group box-2 (HMGB2) and valve calcification in senile degenerative heart valve disease (SDHVD). METHODS: According to the echocardiographic results, patients with calcified heart valves were used as the experimental group and patients without calcified heart valves were used as the control group; blood was drawn for testing, and serum levels of HMGB2 were measured by an enzyme-linked immunosorbent assay. Human heart valve interstitial cells (hVICs) cultured in vitro were randomly divided into two groups. The calcification group was cultured with a medium containing calcification induction solution and cells were induced on days 1, 3, and 5, and the control group was cultured with a standard medium. Expression of bone morphogenetic protein 4 (BMP-4) and HMGB2 in both groups was detected by Western blot. RT-PCR was performed to detect the expression of the HMGB2 gene during calcification. The hVICs were cultured in vitro for 4 days with different concentrations of exogenous HMGB2 (0.01 µg/mL, 0.1 µg/mL, 1 µg/mL, 2 µg/mL), while the control group was cultured with a standard medium and the expression of BMP-4 and NF-κB P65 was detected by Western blot. RESULTS: The serum level of HMGB2 was 7.90 (5.92, 12.39) µg/L, higher than that of 7.06 (5.06, 9.73) µg/L in the valve calcification group in elderly patients with degenerative valve disease (p = 0.005); the differences were statistically significant. In in vitro experiments, the cellular calcification protein BMP-4 and the HMGB2 protein were higher in the calcification group compared to the control group (p < 0.05). Exogenous stimulation of hVICs with HMGB2 was able to upregulate the expression of BMP-4 and NF-κB P65 (p < 0.05). CONCLUSIONS: HMGB2 is correlated with valvular calcification in senile degenerative heart valve disease. The HMGB2 protein may promote the process of SDHVD valve calcification by activating the NF-κB pathway and upregulating the expression of BMP-4.
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Estenosis de la Válvula Aórtica , Calcinosis , Enfermedades de las Válvulas Cardíacas , Humanos , Anciano , Válvula Aórtica/metabolismo , FN-kappa B/metabolismo , Proteína HMGB2/metabolismo , Enfermedades de las Válvulas Cardíacas/metabolismo , Células CultivadasRESUMEN
INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common malignant tumours in the world and has a high mortality rate. However, the pathogenesis of HCC remains unclear. This study aimed to investigate the potential biomarkers of HCC. METHODS: ONCOMINE, HCCDB and THE HUMAN PROTEIN ATLAS were used to identify myelin expression factor 2 (MYEF2) as a potential biomarker for HCC. The Cancer Genome Atlas database was used to further validate and analyse the value of MYEF2. Kaplan-Meier Plotter was used for the prognostic analysis. The COX regression model and Kaplan-Meier method were used to investigate the clinical value of MYEF2 in the prognosis of HCC by reviewing the survival status of patients. Fluorescent quantitative polymerase chain reaction (qPCR) and immunohistochemistry were used to detect the expressions of the MYEF2 mRNA and protein in HCC tissues and cell lines. qPCR and Western blotting were used to validate the efficiency of MYEF2 knockout and overexpression in HCC cells. The invasion and migration abilities regulated by MYEF2 were detected by performing transwell and wound healing assays. RESULTS: MYEF2 is significantly upregulated in HCC and is mainly located in the nucleus of HCC cells. MYEF2 expression is significantly associated with the tumour stage, histological grade and TNM stage. High MYEF2 expression is an independent prognostic factor for patients with HCC. Functionally, elevated MYEF2 facilitated cell migration and invasion in vitro. In contrast, decreased MYEF2 inhibited cell migration and invasion. CONCLUSIONS: MYEF2 may be a novel biomarker with potential diagnosis and prognosis values and as a potential therapeutic target for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas del Tejido Nervioso , Proteínas Represoras , Humanos , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , Pronóstico , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismoRESUMEN
Accumulating evidence has demonstrated the roles of circular RNAs (circRNAs) in hepatocellular carcinoma (HCC); however, their roles in HCC need to be further studied. Through high-throughput human circRNA microarray analysis of HCC and adjacent normal tissues, we identified hsa_circ_0051040 as a novel candidate circRNA for the diagnosis and treatment of HCC. In this study, we found that hsa_circ_0051040 was overexpressed in HCC tissues and cell lines and that its expression was correlated with poor prognosis. Knockdown of hsa_circ_0051040 inhibited the migration, invasion, and proliferation of HCC cells in vitro and in vivo, whereas overexpression of hsa_circ_0051040 had the opposite effects. Moreover, our data demonstrated that hsa_circ_0051040 acted as a sponge for miR-569 to regulate ITGAV expression and induce EMT progression. Our findings indicated that hsa_circ_0051040 promotes HCC development and progression by sponging miR-569 to increase ITGAV expression. Thus, hsa_circ_0051040 is a good candidate as a therapeutic target.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , ARN Circular/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , MicroARNs/genética , MicroARNs/metabolismo , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genéticaRESUMEN
BACKGROUND: Although expression of interleukin (IL)-34 is upregulated in active ulcerative colitis (UC), the molecular function and underlying mechanism are largely unclear. AIM: To investigate the function of IL-34 in acute colitis, in a wound healing model and in colitis-associated cancer in IL-34-deficient mice. METHODS: Colitis was induced by administration of dextran sodium sulfate (DSS), and carcinogenesis was induced by azoxymethane (AOM). Whether the impact of IL-34 on colitis was dependent on macrophages was validated by depletion of macrophages in a murine model. The association between IL-34 expression and epithelial proliferation was studied in patients with active UC. RESULTS: IL-34 deficiency aggravated murine colitis in acute colitis and in wound healing phase. The effect of IL-34 on experimental colitis was not dependent on macrophage differentiation and polarization. IL-34-deficient mice developed more tumors than wild-type mice following administration of AOM and DSS. No significant difference was shown in degree of cellular differentiation in tumors between wild-type and IL-34-deficient mice. IL-34 was dramatically increased in the active UC patients as previously reported. More importantly, expression of IL-34 was positively correlated with epithelial cell proliferation in patients with UC. CONCLUSION: IL-34 deficiency exacerbates colonic inflammation and accelerates colitis-associated carcinogenesis in mice. It might be served as a potential therapeutic target in UC.
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Colitis Ulcerosa , Neoplasias Asociadas a Colitis , Colitis , Animales , Ratones , Colitis/inducido químicamente , Colitis/complicaciones , Colitis/patología , Interleucinas/genética , Colitis Ulcerosa/complicaciones , Carcinogénesis , Azoximetano/toxicidad , Sulfato de Dextran/toxicidad , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: As a new class of non-coding RNAs, circRNAs have been recently reported to be involved in the tumorigenesis and progression of human cancers. In the current study, we attempted to explore the potential function of a novel circRNA (hsa_circ_0013290) in hepatocellular carcinoma (HCC). METHODS: Relative hsa_circ_0013290 expression was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The subcellular location of hsa_circ_0013290 was performed by RNA subcellular isolation and fluorescence in situ hybridization (FISH) assays. The effect of hsa_circ_0013290 on proliferation was detected by Cell Counting Kit-8 (CCK-8) assays. The effect of hsa_circ_0013290 on cell cycle distribution and apoptosis was detected by flow cytometry. The invasion and migration abilities of hsa_circ_0013290 were detected by transwell assays. RESULTS: Hsa_circ_0013290 is significantly upregulated in HCC cell lines and mainly located in cytoplasm of HCC cells. Hsa_circ_0013290 overexpression promotes cell invasion and migration and inhibits cell apoptosis. In contrast, hsa_circ_0013290 knockdown impedes cell invasion and migration and accelerates cell apoptosis. However, hsa_circ_0013290 did not affect cell proliferation. CONCLUSIONS: Hsa_circ_0013290 is overexpressed in HCC cell lines and is mainly located in the cytoplasm of HCC cells. Hsa_circ_0013290 promotes cell invasion and migration, and inhibits cell apoptosis.