MicroRNA-361-5p Inhibits Tumorigenesis and the EMT of HCC by Targeting Twist1.

Liang-Chun Yin,Li-Xin Liu,Jun Weng,Gang Xiao,Xiao-Ping Huang,Ning-Lei Li,Can-Liang Tan,Feng-Jiao Xie,Rui Zhou,Maciej Gagat

doi:10.1155/2020/8891876

Abstract

MicroRNA-361-5p (miR-361-5p) is a tumor suppressor miRNA that is dysregulated in several types of human cancer. However, the functional significance of miR-361-5p in hepatocellular carcinoma (HCC) is unclear. This study explored the biological function of miR-361-5p in regulating the progression of HCC and the underlying molecular mechanism. RT-qPCR analysis showed that miR-361-5p was downregulated in HCC tissues and cell lines. Functional analysis revealed that miR-361-5p acted as a tumor suppressor, inhibiting cell proliferation, migration, and invasion in HCC cell lines. Bioinformatics analyses identified Twist1 as a direct target of miR-361-5p, which was validated by dual-luciferase reporter assays, RT-qPCR, and western blotting. Rescue experiments indicated that Twist1 may mediate the tumor-suppressive effect of miR-361-5p in HCC cells, and this was supported by the effect of miR-361-5p on inhibiting the epithelial-mesenchymal transition (EMT) by targeting Twist1. This study is the first to suggest that miR-361-5p inhibits tumorigenesis and EMT in HCC by targeting Twist1. These findings are valuable for the diagnosis and clinical management of HCC.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and a major threat to human health [1,2,3]
To determine the biological role of miR-361-5p in HCC, the miR-361-5p expression in HCC tissues and cell lines was detected by RT-qPCR, and its expression in HCC tumor tissues and adjacent nontumorous tissues was detected by In Situ Hybridization (ISH) (Figure 1(a))
The miR-361-5p expression was markedly lower in HCC cell lines (Hep3B, HepG2, and MHCC-97H) than in normal human hepatic LO2 cells (Figure 1(e))

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and a major threat to human health [1,2,3]. Despite advances in the treatment of HCC in recent decades, HCC remains the third leading cause of cancer-related mortality worldwide, with nearly 600,000 deaths from HCC each year [4, 5]. MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression by promoting mRNA degradation or by inhibiting mRNA translation [7]. The microRNAs inhibit gene expression via by binding to the 3′ -UTR (3′-untranslated region) of the target mRNA [8,9,10,11]. The miRNAs can regulate cancer cell proliferation, differentiation, apoptosis, invasion, migration, and angiogenesis by inhibiting the translation or transcription of their target mRNAs [12]. MiRNAs have received increasing attention for their potential use in cancer diagnosis and treatment [13]. This study investigated the biological function of miR-361-5p in regulating the progression of HCC and explored the underlying molecular mechanism

Methods

Results

Conclusion