Zou Lei, Sun Peng, Zhang Lei
Department of Gastroenterology, Zibo Central Hospital, Zibo 255036, Shandong Province, China.
J Oncol. 2021 Aug 18;2021:5391977. doi: 10.1155/2021/5391977. eCollection 2021.
Drug resistance is a major challenge for hepatocellular carcinoma (HCC) treatment in a clinic, which limits the therapeutic effect of the chemotherapeutic drugs, including cisplatin (CDDP), in this disease. Mounting evidence has identified that miRNAs dysfunction is related to the resistance of tumor cells to CDDP, and miR-651-3p has been identified as a tumor inhibitor to suppress the progression of multiple tumors. However, the role of miR-651-3p in HCC remains unclear. In this study, the relative expression of miR-651-3p in HCC tissues and cell lines were measured, and the functions of miR-651-3p were also observed by CCK-8 assay, flow cytometry assay, and Western blot. Moreover, the downstream target of miR-651-3p was predicted and verified via TargetScan and dual-luciferase reporter assay, and its functions were also investigated. The results showed that miR-651-3p was significantly downregulated in HCC tissues and cell lines, and the decreased miR-651-3p was also observed in CDDP-induced cells. miR-651-3p upregulation could effectively inhibit the proliferation and induce the apoptosis of R-HepG2. It was also found that ATG3 was a downstream target of miR-651-3p, and ATG3 was highly upregulated in HCC tissues. Moreover, the upregulated ATG3 could partly reverse the effects of miR-651-3p on R-HepG2. Besides, miR-651-3p involved the autophagy pathway of the HCC cells via targeting ATG3. In conclusion, miR-651-3p could regulate the autophagy to enhance the sensitivity of HepG2 cells to CDDP via targeting ATG3.
耐药性是临床肝细胞癌（HCC）治疗面临的主要挑战，它限制了包括顺铂（CDDP）在内的化疗药物在该疾病中的治疗效果。越来越多的证据表明，miRNA功能障碍与肿瘤细胞对CDDP的耐药性有关，并且miR-651-3p已被确定为一种肿瘤抑制因子，可抑制多种肿瘤的进展。然而，miR-651-3p在HCC中的作用仍不清楚。在本研究中，检测了miR-651-3p在HCC组织和细胞系中的相对表达，并通过CCK-8检测、流式细胞术检测和蛋白质印迹法观察了miR-651-3p的功能。此外，通过TargetScan和双荧光素酶报告基因检测预测并验证了miR-651-3p的下游靶点，并对其功能进行了研究。结果表明，miR-651-3p在HCC组织和细胞系中显著下调，在CDDP诱导的细胞中也观察到miR-651-3p降低。miR-651-3p上调可有效抑制R-HepG2的增殖并诱导其凋亡。还发现ATG3是miR-651-3p的下游靶点，且ATG3在HCC组织中高度上调。此外，上调的ATG3可部分逆转miR-651-3p对R-HepG2的影响。此外，miR-651-3p通过靶向ATG3参与了HCC细胞的自噬途径。总之，miR-651-3p可通过靶向ATG3调节自噬，增强HepG2细胞对CDDP的敏感性。
