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1.
Technol Cancer Res Treat ; 21: 15330338221077803, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35167383

RESUMO

Introduction: Renal cancer is one of the most common cancers in the world, but the effect of therapies on advanced renal cancer has not improved for decades. Ferroptosis is an emerging type of programmed cell death and has been proved to play a vital role in many kinds of cancers. However, the mechanisms of ferroptosis regulated by long noncoding RNA (lncRNA) in the context of renal cancer was still unknown. Methods: We used bioinformation analysis to identify SLC16A1-AS1 as a survival-related lncRNA in renal cancer. The expression levels of SLC16A1-AS1 and microRNA-143-3p (miR-143-3p) were detected by quantitative reverse transcription-polymerase chain reaction. Cell counting kit-8 assay, 5-bromo-2'-deoxyuridine proliferation assay, and colony-formation assay were performed to evaluate cell viability and proliferation. Wound-healing assay and transwell assay were used to examine cell invasive and migration capacity. Dual-luciferase reporter assay and RNA-binding protein immunoprecipitation were used to identify the interaction among SLC16A1-AS1, miR-143-3p, and the target protein solute carrier family 7 membrane 11 (SLC7A11). Reduced glutathione and glutathione and lipid peroxidation measurements were carried out to evaluate the level of ferroptosis, and the expression levels of ferroptosis-related proteins were analyzed by western blot. Results: Our study revealed that SLC16A1-AS1 has high expression and was associated with overall survival in renal cancer. Knockdown SLC16A1-AS1 inhibited cell viability, proliferation, and migration of renal cancer cells. Furthermore, it was demonstrated that SLC16A1-AS1 served as a sponge of miR-143-3p, and knockdown SLC16A1-AS1 significantly increased the enrichment of miR-143-3p. And then, SLC7A11 was identified as the target protein of miR-143-3p, and overexpression miR-143-3p remarkably inhibited the expression of SLC7A11. Moreover, knockdown SLC16A1-AS1 could aggravate this effect. Finally, through inhibiting SLC7A11 expression, silencing SLC16A1-AS1 induced ferroptosis via increasing miR-143-3p. Conclusion: The present results suggest that silencing lncRNA SLC16A1-AS1 can induce ferroptosis through miR-143-3p/SLC7A11 signaling in renal cancer. Our study provided a novel view into the pathogenesis and treatment strategy of RCC.


Assuntos
Carcinoma de Células Renais , Ferroptose , Neoplasias Renais , MicroRNAs , RNA Longo não Codificante , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
2.
Oncol Lett ; 22(5): 781, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34594422

RESUMO

Renal cell carcinoma (RCC) is a most common malignant tumor in the genitourinary system. Studies have shown that Lycorine has promising anticancer activities with minor side effects. However, the effect of lycorine on the proliferation of RCC cells and its underlying anti-tumor mechanism have not yet been fully elucidated. The human renal cancer cell lines 786-O, A498 and Caki-1 were cultured and treated with different concentrations of lycorine or ferrostatin-1, a ferroptosis inhibitor. Cell viability and colony formation assays were used to measure cell proliferation. The 5-, 12- and 15-HETE hydroxyeicosatetraenoic acid (HETE) and MDA levels, as well as the reduced to oxidized glutathione (GHS/GSSG) ratio, were analyzed. Western blot analysis was used to detect the expression of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long chain family member 4 (ACSL4), which are key markers of ferroptosis. Transmission electron microscopy was used to observe the morphological features associated with ferroptosis. Lycorine was found to inhibit the proliferation of RCC cells. After lycorine treatment, the expression levels of GPX4 in RCC cells decreased, whereas those of ACSL4 increased. Lycorine induced the expression of 5-HETE, 12-HETE, 15-HETE and MDA in RCC cells, and reduced the GSH/GSSG ratio. In addition, ferrostatin-1 could prevent lycorine-induced ferroptosis in RCC cells.

3.
Biomed Pharmacother ; 83: 593-601, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27459115

RESUMO

Increasing study reports that Wnt/ß-catenin signaling pathway plays an essential role in numerous cancers growth, progression and metastasis. Aberrant miR-940 expression has been studied in gastric and breast cancer. However, the molecular mechanism of miR-940 enhancing proliferation and metastatic ability in human pancreatic carcinoma is far from to know. Real-time PCR was used to quantify miR-940 expression. Luciferase reporter assays here were performed to verify the activity of Wnt/ß-catenin signaling pathway and targeting gene relationships, and immunofluorescence assay was applied to observe ß-catenin expressed intensity. Bioinformatics analysis together with in vivo and vitro functional analysis indicated the potential targeting genes of miR-940. Specimens from 15 pairs of patients with human pancreatic carcinoma were involoved to confirm the relationship between miR-940 expression and the GSK3ß/sFRP1 through real-time PCR and western blot assays. Bioinformatics combined with cell luciferase function researches determined the possible regulation of miR-940 on the 3'-UTR of the GSK3ß and sFRP1 genes, resulting in the Wnt/ß-catenin signaling activation. Further, miR-940 knockdown significantly recovered GSK3ß and sFRP1 expression and relieved Wnt/ß-catenin-mediated cell invasion, migration, metastasis and proliferation. The ectopic up-regulation of miR-940 significantly suppressed GSK3ß/sFRP1 expression and promoted pancreatic carcinoma proliferation and invasion. Our study suggested mechanistic relationship between miR-940 and Wnt/ß-catenin in the development and progression of pancreatic carcinoma through regulation of GSK3ß and sFRP1.


Assuntos
Glicogênio Sintase Quinase 3 beta/metabolismo , MicroRNAs/metabolismo , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/genética , Proteínas/metabolismo , Animais , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Neoplasias Pancreáticas/patologia , Via de Sinalização Wnt/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias Pancreáticas
4.
PLoS One ; 7(8): e43452, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22912877

RESUMO

MicroRNAs have been implicated in the regulation of several cellular signaling pathways of colorectal cancer (CRC) cells. Although emerging evidence proves that microRNA (miR)-106a is expressed highly in primary tumor and stool samples of CRC patients; whether or not miR-106a mediates cancer metastasis is unknown. We show here that miR-106a is highly expressed in metastatic CRC cells, and regulates cancer cell migration and invasion positively in vitro and in vivo. These phenotypes do not involve confounding influences on cancer cell proliferation. MiR-106a inhibits the expression of transforming growth factor-ß receptor 2 (TGFBR2), leading to increased CRC cell migration and invasion. Importantly, miR-106a expression levels in primary CRCs are correlated with clinical cancer progression. These observations indicate that miR-106a inhibits the anti-metastatic target directly and results in CRC cell migration and invasion.


Assuntos
Movimento Celular/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Células HT29 , Humanos , Estimativa de Kaplan-Meier , Masculino , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Interferência de RNA , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante Heterólogo
5.
World J Gastroenterol ; 18(21): 2640-8, 2012 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-22690072

RESUMO

AIM: To evaluate the effect of nigericin on colorectal cancer and to explore its possible mechanism. METHODS: The human colorectal cancer (CRC) cell lines HT29 and SW480 were treated with nigericin or oxaliplatin under the conditions specified. Cell viability assay and invasion and metastasis assay were performed to evaluate the effect of nigericin on CRC cells. Sphere-forming assay and soft agar colony-forming assay were implemented to assess the action of nigericin on the cancer stem cell properties of CRC cells undergone epithelial-mesenchymal transition (EMT). RESULTS: Compared with oxaliplatin, nigericin showed more toxicity for the HT29 cell line (IC50, 12.92 ± 0.25 µmol vs 37.68 ± 0.34 µmol). A similar result was also obtained with the SW116 cell line (IC50, 15.86 ± 0.18 µmol vs 41.02 ± 0.23 µmol). A Boyden chamber assay indicated that a significant decrease in the number of HT29 cells migrating through polyvinylidene fluoride membrane was observed in the nigericin-treated group, relative to the vehicle-treated group [11 ± 2 cells per high-power field (HPF) vs 19.33 ± 1.52 cells per HPF, P < 0.05]. Compared to the control group, the numbers of HT29 cells invading through the Matrigel-coated membrane also decreased in the nigericin-treated group (6.66 ± 1.52 cells per HPF vs 14.66 ± 1.52 cells per HPF, P < 0.05). Nigericin also reduced the proportion of CD133+ cells from 83.57% to 63.93%, relative to the control group (P < 0.05). Nigericin decreased the number of spheres relative to the control group (0.14 ± 0.01 vs 0.35 ± 0.01, P < 0.05), while oxaliplatin increased the number of spheres relative to the control group (0.75 ± 0.02 vs 0.35 ± 0.01; P < 0.05). Nigericin also showed a decreased ability to form colonies under anchorage-independent conditions in a standard soft agar assay after 14 d in culture, relative to the control group (1.66 ± 0.57 vs 7 ± 1.15, P < 0.05), whereas the colony numbers were higher in the oxaliplatin group relative to the vehicle-treated controls (14.33 ± 0.57 vs 7 ± 1.15, P < 0.05). We further detected the expression of E-cadherin and vimentin in cells treated with nigericin and oxaliplatin. The results showed that HT29 cells treated with nigericin induced an increase in E-cadherin expression and a decrease in the vimentin expression relative to vehicle controls. In contrast, oxaliplatin downregulated the expression of E-cadherin and upregulated the expression of vimentin in HT29 cells relative to vehicle controls. CONCLUSION: This study demonstrated that nigericin could partly reverse the EMT process during cell invasion and metastasis.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Nigericina/farmacologia , Antígeno AC133 , Antibacterianos/farmacologia , Antígenos CD/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Citometria de Fluxo/métodos , Glicoproteínas/metabolismo , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Células-Tronco Neoplásicas/citologia , Compostos Organoplatínicos/farmacologia , Oxaliplatina , Peptídeos/metabolismo , Vimentina/metabolismo
6.
Asian Pac J Cancer Prev ; 13(1): 117-22, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22502652

RESUMO

AIM: To elucidate the effects of hyperthermic CO2 pneumoperitoneum on human gastric AGS cells. METHODS: Based on a newly devised in vitro study model, we evaluated the anti-cancer effects of HT-CO2 (42-44 degrees C for 2-4h) on human gastric cancer cells, and also the corresponding mechanisms. RESULTS: HT-CO2 (42-44 degrees C for 2-4h) severely inhibited cell proliferation as assessed by Cell Counting Kit-8 assay, while inducing apoptosis in a temperature- and time-dependent manner demonstrated by annexin-V/PI flow cytometry and morphological analysis (Hoechst/PI fluorescence). In addition, it was found that HT-CO2 (42-44 degrees C for 2-4h) promoted the up-regulation of Bax by western blotting. Significantly, it could also suppress gastric cancer cell invasion and metastasis by in vitro invasion and motility assay. CONCLUSION: In conclusion, HT-CO2 had an efficacious cytotoxic effect on gastric cancer cells through Bax-induced mitochondrial apoptotic signaling. Our studies indicate that it may serve as a potential therapy for peritoneal carcinomatosis of gastric cancer. Further investigations in vivo using animal models are now urgently needed.


Assuntos
Adenocarcinoma/prevenção & controle , Apoptose/efeitos dos fármacos , Dióxido de Carbono/uso terapêutico , Hipertermia Induzida , Pneumoperitônio/prevenção & controle , Neoplasias Gástricas/prevenção & controle , Adulto , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Citometria de Fluxo , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2
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