MicroRNA-143 inhibits tumorigenesis in hepatocellular carcinoma by downregulating GATA6.

Feng Xue,Boqing Wang,Lin Xu,Jiwei Yin

doi:10.3892/etm.2017.4348

Abstract

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 in vivo (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.

Highlights

Human hepatocellular carcinomas (HCC) are among the most aggressive types of tumor worldwide, with a notably low five‐year survival rate of 18% [1]
The current study set out to determine whether the expression of miR‐143 in in vitro HCC cell lines, as well as in in vivo HCC human samples was altered compared with normal liver cells
The Reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) results showed that miR‐143 expression was significantly reduced in seven HCC cell lines (SMMC‐7721, Hep3B, HepG2, Huh7, Bel7402, MHCC97‐H and SK‐Hep1) compared with a normal liver cell line (L02; P

Summary

Introduction

Human hepatocellular carcinomas (HCC) are among the most aggressive types of tumor worldwide, with a notably low five‐year survival rate of 18% [1]. Most HCC patients are diagnosed in the late stages and the prognosis is poor, largely due to. An exact mapping of HCC oncogenesis and metastasis has not yet been established, but numerous previous studies have indicated that miRNAs serve key functions in HCC development [4,5,6,7,8]. MiR‐1188 can directly target Bcl‐2 and Sp1, inhibiting cell proliferation, invasion and migration, and resulting in attenuated growth of HCC cells in vivo [7]. Another study reports that miR‐148b can regulate cancer stem cell properties in HCC by directly targeting Neuropilin‐1, which is a transmembrane receptor implicated as a key factor in initiating angiogenesis and metastasis [8]

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Results

Conclusion