Department of Liver and Infectious Diseases, Liver Disease Research Center, The Second People's Hospital of Yunnan Province, Kunming, P.R. China.
School of Medicine, Yunnan University, Kunming, P.R. China.
Oncol Res. 2018 May 7;26(4):557-563. doi: 10.3727/096504017X15000784459799. Epub 2017 Jul 21.
Hepatocellular carcinoma (HCC) is a disease with poor prognosis rates and ineffective therapeutic options. Previous studies have reported the involvement of mitogen-inducible gene 6 (MIG-6) as a negative regulator in tumor formation. MicroRNAs (miRNAs) play crucial roles in the development of different types of cancer. However, the underlying mechanisms of miRNAs in HCC are poorly understood. This study was aimed to investigate the role of miR-374a in HCC and its role in the regulation of expression of MIG-6. The results showed that MIG-6 overexpression significantly inhibited cell viability of HepG2 cells after 4 days posttransfection. Moreover, MIG-6 was a direct target of miR-374a, and the expression of MIG-6 was remarkably downregulated by the overexpression of miR-374a in HepG2 cells. Furthermore, we found that overexpression of miR-374a promoted cell viability; however, the protective effect was abolished by MIG-6 overexpression. In addition, overexpression of miR-374a activated the EGFR and AKT/ERK signaling pathways by regulation of MIG-6. Our findings suggest that miR-374a could promote cell viability by targeting MIG-6 and activating the EGFR and AKT/ERK signaling pathways. These data provide a promising therapeutic strategy for HCC treatment.
肝细胞癌 (HCC) 是一种预后不良且治疗选择效果不佳的疾病。先前的研究报告称,有丝分裂原诱导基因 6 (MIG-6) 作为肿瘤形成的负调节剂参与其中。microRNAs (miRNAs) 在不同类型癌症的发展中起着至关重要的作用。然而,miRNAs 在 HCC 中的潜在机制尚不清楚。本研究旨在探讨 miR-374a 在 HCC 中的作用及其对 MIG-6 表达调控的作用。结果表明,MIG-6 过表达后,转染后 4 天 HepG2 细胞的细胞活力明显受到抑制。此外,MIG-6 是 miR-374a 的直接靶标,miR-374a 在 HepG2 细胞中的过表达显著下调了 MIG-6 的表达。此外,我们发现 miR-374a 的过表达促进了细胞活力;然而,MIG-6 的过表达则消除了这种保护作用。此外,miR-374a 通过调节 MIG-6 激活了 EGFR 和 AKT/ERK 信号通路。我们的研究结果表明,miR-374a 可以通过靶向 MIG-6 并激活 EGFR 和 AKT/ERK 信号通路来促进细胞活力。这些数据为 HCC 的治疗提供了一种有前景的治疗策略。