MiR‐124‐3p availability is antagonized by LncRNA‐MALAT1 for Slug‐induced tumor metastasis in hepatocellular carcinoma

Rong‐Jun Cui,Chi Liu,Jie‐Bing Tang,Zheng‐Yuan Jiang,Yu‐Cui Lin,Yu‐Jia Pan,Xiu‐Lan Zheng,Jia‐Hui Wan,Jia‐Lin Fan,Wei Wang,Xiao‐Guang Yu

doi:10.1002/cam4.2482

Abstract

BackgroundAs an oncogene, long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) can promote tumor metastasis. Hyperexpression of MALAT1 has been observed in many malignant tumors, including hepatocellular carcinoma (HCC). However, the role and mechanism of MALAT1 in HCC remain unclear.MethodsThirty human HCC and paracancerous tissue specimens were collected, and the human hepatoma cell lines Huh7 and HepG2 were cultured according to standard methods. MALAT1 and Snail family zinc finger (Slug) expression were measured by real‐time PCR, immunohistochemistry, and western blotting. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay verified the direct interaction between miR‐124‐3p and Slug(SNAI2) or MALAT1. Wound healing and transwell assays were performed to examine invasion and migration, and a subcutaneous tumor model was established to measure tumor progression in vivo.ResultsMALAT1 expression was upregulated in HCC tissues and positively correlated with Slug expression. MALAT1 and miR‐124‐3p bind directly and reversibly to each other. MALAT1 silencing inhibited cell migration and invasion. miR‐124‐3p inhibited HCC metastasis by targeting Slug.ConclusionsMALAT1 regulates Slug through miR‐124‐3p, affecting HCC cell metastasis. Thus, the MALAT1/miR‐124‐3p/Slug axis plays an important role in HCC.

Highlights

Liver cancer is the most common solid cancer worldwide, especially in China.[1]
We identified a Long noncoding RNAs (lncRNAs) signature for metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1), which could act as a potential independent biomarker for prognostic hepatocellular carcinoma (HCC) predictions
We found that high MALAT1 expression was negatively correlated with disease‐ free survival (DFS) in HCC patients based on TCGA data and negatively correlated with DFS (Figure 1E)

Summary

| INTRODUCTION

Liver cancer is the most common solid cancer worldwide, especially in China.[1]. This disease is a major health problem, with more than 841 000 new cases and 782 000 deaths annually worldwide.[2]. We show that the lncRNA MALAT1 is upregulated in HCC tissues and correlated with poor prognosis in this study. The experimental results show that MALAT1 promotes HCC cell migration and invasion as a competing endogenous RNA (ceRNA) for miR‐124‐3p, thereby blocking its association with its target mRNA, namely, Snail family zinc finger (Slug). These results show that MALAT1 is an oncogenic HCC tumorigenesis gene and may be an effective candidate gene for HCC diagnosis and therapy. RNA (including miRNA) was extracted using a TRIzol kit (Life Technologies) according to the product instructions. The relative fold change in mRNA expression was calculated according to the 2−ΔΔCt method

| MATERIALS AND METHODS

Findings

| DISCUSSION