<p>Ovarian cancer (OC) is a type of gynecological cancer, characterized by a high mortality rate. MicroRNAs (miRNAs) and cell autophagy are associated with the chemoresistance of tumors. The purpose of this study was to investigate the role of miR-675-5p in cisplatin (DDP) resistance in OC cells and its related mechanism. We collected OC tissues and paracancerous tissues. The OC cell line A2780 and the DDP-resistant cell line A2780/DDP were used for the study. RT-qPCR, Western blot and immunofluorescence were used to detect the expression of related genes and proteins. Cell proliferation and apoptosis were evaluated by CCK-8 assay and flow cytometry. Furthermore, the effect of miR-675-5p on the progression of OC was investigated in a xenograft model of nude mice. In this research, miR-675-5p expression was significantly increased in OC tissues and A2780/DDP cells. The suppression of miR-675-5p in A2780/DDP cells resulted in a significant reduction in DDP resistance. Further study revealed that miR-675-5p inhibited TSC2 expression in OC cells by binding to the TSC2 3’UTR, thereby activating the mTOR signaling pathway and promoting autophagy in A2780/DDP cells. Knocking down miR-675-5p suppressed DDP resistance in A2780/DDP cells through TSC2/mTOR axis, while overexpressing miR-675-5p suppressed DDP sensitivity in A2780 cells through TSC2. The tumor volume was decreased after injection of miR-675-5p-knockdown A2780/DDP cells in vivo. Knocking down miR-675-5p can inhibit the mTOR signaling pathway and autophagy through TSC2, thereby reducing the DDP resistance of OC cells. This may provide a potential therapeutic target for OC.</p>

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miR-675-5p regulation of autophagy by TSC2 promotes cisplatin resistance in ovarian cancer

  • Tao Yang,
  • Yuan Liu,
  • Hong Liu,
  • Hongjun Zhang,
  • Yi Zhao,
  • Ande Luo,
  • Minjie He

摘要

Ovarian cancer (OC) is a type of gynecological cancer, characterized by a high mortality rate. MicroRNAs (miRNAs) and cell autophagy are associated with the chemoresistance of tumors. The purpose of this study was to investigate the role of miR-675-5p in cisplatin (DDP) resistance in OC cells and its related mechanism. We collected OC tissues and paracancerous tissues. The OC cell line A2780 and the DDP-resistant cell line A2780/DDP were used for the study. RT-qPCR, Western blot and immunofluorescence were used to detect the expression of related genes and proteins. Cell proliferation and apoptosis were evaluated by CCK-8 assay and flow cytometry. Furthermore, the effect of miR-675-5p on the progression of OC was investigated in a xenograft model of nude mice. In this research, miR-675-5p expression was significantly increased in OC tissues and A2780/DDP cells. The suppression of miR-675-5p in A2780/DDP cells resulted in a significant reduction in DDP resistance. Further study revealed that miR-675-5p inhibited TSC2 expression in OC cells by binding to the TSC2 3’UTR, thereby activating the mTOR signaling pathway and promoting autophagy in A2780/DDP cells. Knocking down miR-675-5p suppressed DDP resistance in A2780/DDP cells through TSC2/mTOR axis, while overexpressing miR-675-5p suppressed DDP sensitivity in A2780 cells through TSC2. The tumor volume was decreased after injection of miR-675-5p-knockdown A2780/DDP cells in vivo. Knocking down miR-675-5p can inhibit the mTOR signaling pathway and autophagy through TSC2, thereby reducing the DDP resistance of OC cells. This may provide a potential therapeutic target for OC.