MicroRNA-143 inhibits tumorigenesis in hepatocellular carcinoma by downregulating GATA6

Abstract

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.

Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers

“…Similarly, many studies have shown that miRNAs play a key role in the development of HCC . In HCC, miR‐143 can reduce the proliferation and invasion rate of tumor cells by targeting to reduce the expression level of the GATA6 gene in its downstream target and play a role in inhibiting HCC . As of now, there are relatively few studies on GATA6 and HCC and CCA.…”

Efficacy of Plasma microRNA-143 and microRNA-550a as Potential Diagnostic and Prognostic Biomarkers for Chronic Hepatitis and Hepatocellular Carcinoma in Egyptian Patients

“…The first study to investigate the role of miR-143 in HCC was done recently where the researchers exploited the different cellular pathways that could play important role in the HCC pathogenesis and found that GATA6 was the downstream target for miR-143, where its Overexpression will oppose the cancer suppressor effect of miR-143 thus increasing the tumor invasion in rats [21]. We found that the expression level of plasma miR-550a was significantly lower in HCC than HCV patients.…”

Deregulated GATA6 modulates stem cell‐like properties and metabolic phenotype in hepatocellular carcinoma

“…In one study, miR143 was found downregulated in HCC and that GATA6 was identified as a downstream target. 30 Yet the other study which focused on miR181 showed that GATA6 is a downstream target, and functionally miR181 enhanced EpCAM expression, spheroid formation and in vivo tumorigenicity of HCC. 31 In this present study, we investigated the direct functional effects of independent manipulation of GATA6 in HCC.…”

“…While two previous studies provided indirect clues on the participation of GATA6 in liver cancer, the speculated role of GATA6 based on the findings from the two studies did not appear in line with each other. In one study, miR143 was found downregulated in HCC and that GATA6 was identified as a downstream target . Yet the other study which focused on miR181 showed that GATA6 is a downstream target, and functionally miR181 enhanced EpCAM expression, spheroid formation and in vivo tumorigenicity of HCC .…”