Intravenous drugs dispensing center, Ganzhou People's Hospital , Ganzhou, Jiangxi, China.
Department of Pharmacy, The FirstPeople's Hospital of Xiantao , Xiantao, Hubei Province, China.
Biosci Biotechnol Biochem. 2020 Aug;84(8):1645-1651. doi: 10.1080/09168451.2020.1760784. Epub 2020 May 7.
Oxaliplatin (L-OHP) is one of the effective chemotherapeutic drugs for colorectal cancer (CRC). Further investigation into the molecular mechanism of chemoresistance could improve outcomes for patients with colorectal cancer. Recently, microRNAs have been reported as a key in drug resistance of tumors. In this study, we aimed to investigate the effects of miR-153-5p in L-OHP-resistant CRC cells, and its underlying mechanism. Downregulation of miR-153-5p was observed in CRC cells, while upregulation of miR-153-5p enhances the chemosensitivity of CRC/L-OHP cells. The autophagy of CRC/L-OHP cells was markedly increased after exposure to L-OHP but abolished by the upregulation of miR-153-5p. Dual-luciferase reporter assays validated that Bcl-2 was a direct target of miR-153-5p. In conclusion, our data suggested that miR-153-5p was a mediator of cisplatin resistance in colorectal cancer by affecting Bcl-2-mediated autophagy, indicating a new therapeutic target for CRC treatment.
奥沙利铂（L-OHP）是结直肠癌（CRC）的有效化疗药物之一。进一步研究化疗耐药的分子机制可以改善结直肠癌患者的预后。最近，microRNAs 被认为是肿瘤耐药的关键。在本研究中，我们旨在探讨 miR-153-5p 在 L-OHP 耐药 CRC 细胞中的作用及其潜在机制。在 CRC 细胞中观察到 miR-153-5p 的下调，而 miR-153-5p 的上调增强了 CRC/L-OHP 细胞的化疗敏感性。CRC/L-OHP 细胞在接触 L-OHP 后自噬明显增加，但 miR-153-5p 的上调可消除自噬。双荧光素酶报告基因实验验证了 Bcl-2 是 miR-153-5p 的直接靶基因。总之，我们的数据表明，miR-153-5p 通过影响 Bcl-2 介导的自噬来介导结直肠癌对顺铂的耐药性，为 CRC 的治疗提供了新的治疗靶点。
