Silencing of microRNA-210 inhibits the progression of liver cancer and Hepatitis B virus-associated liver cancer via targeting EGR3

Abstract

Background: This study was aimed to investigate the regulatory role of microRNA-210 (miRNA-210) on the progression of liver cancer and Hepatitis B virus (HBV)-associated liver cancer. Methods: The expression of miRNA-210 was detected in liver tissues of HBV-associated cirrhosis and liver cancer, and in HepG2 and HepG2.2.15 cells by qRT-PCR. MiRNA-210 was silenced in HepG2 and HepG2.2.15 cells by the transfection of miRNA-210 inhibitor. The cell viability and apoptosis was detected by MTT assay and Annexin V-fluorescein isothiocyanate/propidium iodide staining, respectively. The protein expression of EGR3 was detected by Western blot. The regulatory relationship between EGR3 and miRNA-210 was predicted by TargetScan and identified by Dual luciferase reporter gene assay.Results: MiRNA-210 was overexpressed in the liver tissues of HBV-associated cirrhosis and liver cancer, and in HepG2 and HepG2.2.15 cells (P < 0.05). Silencing of miRNA-210 inhibited the viability and promoted the apoptosis of HepG2 and HepG2.2.15 cells (P < 0.05). EGR3 was a target of miRNA-210, which was down-regulated in the liver tissues of HBV-associated cirrhosis and liver cancer, and in HepG2 and HepG2.2.15 cells (P < 0.05). Silencing of miRNA-210 increased the mRNA and protein expression of EGR3 (P < 0.05). Silencing of EGR3 reversed the anti-tumor effect of miRNA-210 inhibitor on HepG2 and HepG2.2.15 cells (P < 0.05).Conclusions: Silencing of miRNA-210 inhibits the progression of liver cancer and HBV-associated liver cancer via up-regulating EGR3.

miR-328-3p overexpression attenuates the malignant proliferation and invasion of liver cancer via targeting Endoplasmic Reticulum Metallo Protease 1 to inhibit AKT phosphorylation

“…The results showed that miR-34a functions as a negative regulator of glucose metabolism and might be a novel marker for liver cancer prognosis. Li et al reported that mirRNA-210 silence exerted inhibition effect in the progression of liver cancer and hepatitis B virus-associated liver cancer via targeting EGR3 (7).…”

miRNAs in Liver Cancer

“…EGR3 was shown to be the target of miRNA-210, contrary to miRNA-210 the expression of EGR3 was downregulated in HBV-associated liver cirrhosis and liver cancer. In general, its role, like the role of miRNA-196a and miRNA-184, may be in proliferation promotion, and it is hard to assume whether the described mechanism with involvement in EGR3 regulation is specific for HBV-associated liver cancer, as far as EGR3 is known to be decreased in other cancers, like in head and neck cancers and gastric cancer [72]. miRNA-210 was also shown to be involved in bile acid-induced cholestatic liver injury through its direct target MLL4 (the histone methyltransferase mixed-lineage leukemia-4).…”

Hepatitis B virus–induced hepatocarcinogenesis: A virological and oncological perspective

“…38 However, negative feedback of microRNA-210 silencing in the HepG2 and HepG2.2.15 cells for apoptosis promotion is likely to inhibit HCC progression. 39…”