Xue Feng, Yin Jiwei, Xu Lin, Wang Boqing
Department of Hepatopancreatobiliary Surgery, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China.
Exp Ther Med. 2017 Jun;13(6):2667-2674. doi: 10.3892/etm.2017.4348. Epub 2017 Apr 18.
MicroRNAs serve a critical role in human hepatocellular carcinoma (HCC) progression. However, the exact role of microRNA-143 (miR-143) in HCC remains unclear. The current study investigates the molecular mechanism of miR-143 in HCC. In cultured HepG2 and Bel7402 cell lines, miR-143 levels were raised by lentivirus transduction. This significantly inhibited HCC progression in terms of cell invasion and proliferation in both HepG2 and Bel7402 cell lines (P<0.05). MiR-143 also significantly decreased tumor implantation (P<0.05). Regulation of miR-143 on its direct target, GATA-binding factor 6 (GATA6), was investigated by multiple strategies, including dual-luciferase assay, quantitative polymerase chain reaction and western blot analysis. The results indicated that miR-143 was downregulated in both HCC cell lines and human tumors. GATA6 was identified as the downstream target of miR-143 in HCC, and overexpressing GATA6 was able to counter the tumor-suppressive effect of miR-143 on HCC in HepG2 and Bel7402 cells by significantly increasing proliferation and invasion rates (P<0.05). Therefore, a novel epigenetic pathway was identified in which miR-143 may suppress the malignancy of HCC by targeting GATA6.
微小RNA在人类肝细胞癌（HCC）进展中发挥关键作用。然而，微小RNA-143（miR-143）在HCC中的确切作用仍不清楚。本研究探讨miR-143在HCC中的分子机制。在培养的HepG2和Bel7402细胞系中，通过慢病毒转导提高miR-143水平。这在HepG2和Bel7402细胞系中均显著抑制了HCC进展，包括细胞侵袭和增殖（P<0.05）。miR-143还显著降低了肿瘤种植（P<0.05）。通过多种策略研究了miR-143对其直接靶点GATA结合因子6（GATA6）的调控，包括双荧光素酶测定、定量聚合酶链反应和蛋白质印迹分析。结果表明，miR-143在HCC细胞系和人类肿瘤中均下调。GATA6被确定为HCC中miR-143的下游靶点，在HepG2和Bel7402细胞中过表达GATA6能够通过显著提高增殖和侵袭率来对抗miR-143对HCC的肿瘤抑制作用（P<0.05）。因此，确定了一条新的表观遗传途径，其中miR-143可能通过靶向GATA6抑制HCC的恶性程度。
