Deng X J, Zheng H L, Ke X Q, Deng M, Ma Z Z, Zhu Y, Cui Y Y
Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, China; Department of Gastroenterology, The First Affiliated Hospital of Jinan University, China.
Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, China.
Cell Signal. 2021 Aug;84:110016. doi: 10.1016/j.cellsig.2021.110016. Epub 2021 Apr 22.
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.
多药耐药（MDR）是化疗的主要障碍，它会导致化疗无效，而化疗是胃癌（GC）的一种重要治疗策略。微小RNA（miRNA）的异常对于各种肿瘤中MDR的发生和发展至关重要。在本研究中，发现与亲代SGC-7901细胞相比，多药耐药的GC细胞SGC-7901/5-氟尿嘧啶（SGC-7901/5-Fu）中hsa-miR-34a-5p表达降低。在SGC-7901/5-Fu细胞中过表达hsa-miR-34a-5p可促进细胞凋亡，并在化疗后降低细胞迁移和侵袭能力。此外，hsa-miR-34a-5p过表达在体内抑制耐药肿瘤的生长。hsa-miR-34a-5p发挥作用的机制可能包括通过直接结合沉默调节蛋白1（SIRT1）的3'-非翻译区（UTR）来调控SIRT1、P-糖蛋白（P-gp）或多药耐药相关蛋白1（MRP1）的表达。功能获得和缺失实验表明，hsa-miR-34a-5p通过抑制SIRT1、P-gp和MRP1增强MDR GC细胞的化疗敏感性。总之，hsa-miR-34a-5p可通过抑制SIRT1、P-gp或MRP1的表达来逆转GC细胞的MDR。
