Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, China.
Department of Anesthesiology, General Hospital of Ningxia Medical University, Yinchuan, China.
FEBS Open Bio. 2020 Jun;10(6):1021-1030. doi: 10.1002/2211-5463.12838. Epub 2020 Apr 18.
Elucidation of the mechanisms underlying multidrug resistance (MDR) is required to ensure the efficacy of chemotherapy against gastric cancer (GC). To investigate this issue, here we identified that microRNA-765 (miRNA-765) is up-regulated both in MDR GC cell lines and in specimens from patients who are not responding to chemotherapy. In addition, down-regulation of miRNA-765 increased the sensitivity of GC cells to anticancer drugs, whereas its overexpression had the opposite effect. Moreover, miRNA-765 suppressed drug-induced apoptosis and positively regulated the expression of MDR-related genes. Finally, we showed that the basic leucine zipper ATF-like transcription factor 2, a tumor suppressor gene, is the functional target of miRNA-765. In summary, these results suggest that miRNA-765 may promote MDR via basic leucine zipper ATF-like transcription factor 2 in GC cells.
阐明多药耐药（MDR）的机制对于确保胃癌（GC）化疗的疗效至关重要。为了研究这个问题，我们在这里发现，microRNA-765（miRNA-765）在多药耐药 GC 细胞系和对化疗无反应的患者标本中均上调。此外，miRNA-765 的下调增加了 GC 细胞对抗癌药物的敏感性，而其过表达则产生相反的效果。此外，miRNA-765 抑制了药物诱导的细胞凋亡，并正向调节了 MDR 相关基因的表达。最后，我们表明，碱性亮氨酸拉链 ATF 样转录因子 2，一种肿瘤抑制基因，是 miRNA-765 的功能靶标。总之，这些结果表明，miRNA-765 可能通过 GC 细胞中的碱性亮氨酸拉链 ATF 样转录因子 2促进 MDR。
