Upregulation of miR-29a-3p suppresses cisplatin resistance in gastric cancer via targeting ATG7 to restrain autophagy and induces apoptosis
Keywords:
apoptosis, autophagy, cisplatin resistance, gastric cancerAbstract
Background Drug resistance and relapse are the main reasons for malignant gastric cancer. miR-29a-3p is a tumor suppressor in gastric cancer. However, the antitumor function and regulatory mechanism of miR-29a-3p in gastric cancer remain largely unknown. Thus, the aims of this study are investigation of the role of lncRNA DANCR and the molecular mechanism of miR-29a-3p in gastric cancer.
Methods The expression of miR-29a-3p and autophagy-related gene 7 (ATG7) was detected by qRT-PCR. Survival curve was performed by Kaplan-Meier methods. The cell proliferation and apoptosis were measured by Cell counting kit-8 (CCK-8) assay and Annexin-V FITC/PI staining. And the autophagy-related proteins and apoptosis-related proteins were analyzed by western blotting. Besides, the relationship between miR-29a-3p and ATG7 were determined by dual-luciferase reporter system. The xenograft tumor mice were established to detect the effects of miR-29a-3p in vivo. Immunohistochemistry was used to detect the LC3Ⅱ level, and the TUNEL staining was used to calculate apoptotic cells.
Results We found that low expression of miR-29a-3p, and low expression of ATG7 in gastric cancer tissues and cell lines. And low expression of miR-29a-3p positively correlated with poor survival of gastric cancer patients. Moreover, upregulation of miR-29a-3p inhibited cell proliferation, autophagy, and induced cell apoptosis and sensitive to cisplatin. And we predicated and proved that miR-29a-3p inhibited cell proliferation, autophagy, and induced apoptosis and cisplatin-sensitivity by targeting ATG7.
Conclusion Our study demonstrated the anti-tumor role of miR-29a-3p in gastric cancer, and indicated the regulatory mechanism of miR-29a-3p on autophagy of gastric cancer.
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