Journal
CELLULAR SIGNALLING
Volume 84, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2021.110016
Keywords
Gastric cancer; Multidrug resistance; Hsa-miR-34a-5p; SIRT1
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Funding
- Natural Science Research Project of Anhui Universities [KJ2019A0336]
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This study identified that hsa-miR-34a-5p was decreased in multidrug resistant gastric cancer cells and could reverse MDR by promoting apoptosis and inhibiting migration and invasiveness after chemotherapy. The mechanism of hsa-miR-34a-5p may involve the regulation of SIRT1, P-gp, and MRP1, thereby enhancing chemotherapy sensitivity in MDR gastric cancer cells.
Multidrug resistance (MDR) is a major obstacle to chemotherapy, which leads to ineffective chemotherapy, an important treatment strategy for gastric cancer (GC). The abnormality of microRNAs (miRNAs) is critical to the occurrence and progression of MDR in various tumors. In this study, hsa-miR-34a-5p was found to be decreased in multidrug resistant GC cells SGC-7901/5-Fluorouracil (SGC-7901/5-Fu) compared to the parental SGC-7901 cells. Overexpression of hsa-miR-34a-5p in SGC-7901/5-Fu cells promoted apoptosis and decreased migration and invasiveness after chemotherapy. In addition, overexpression of hsa-miR-34a-5p suppressed the growth of drug-resistant tumor in vivo. The mechanism of the effects of hsa-miR-34a-5p could include the regulation of the expression of Sirtuin 1 (SIRT1), P-glycoprotein (P-gp) or Multidrug resistance-related protein 1 (MRP1) through direct binding to the 3'-untranslated region (UTR) of SIRT1. Functional gain-and-loss experiments indicated that hsa-miR-34a-5p enhances the chemotherapy sensitivity of MDR GC cells by inhibiting SIRT1, P-gp and MRP1. In conclusion, hsa-miR-34a-5p can reverse the MDR of GC cells by inhibiting the expression of SIRT1, P-gp or MRP1.
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