Long noncoding RNA NEAT1 promotes cell proliferation, migration, and invasion in hepatocellular carcinoma through interacting with miR-384.

Liying Zhu,Wei Pan,Xing Li,Chengcheng Li,Guoqi Liu,Nenghong Yang

doi:10.1002/jcb.27499

Abstract

It was reported that long non‐coding RNA nuclear‐enriched abundant transcript 1 (NEAT1) is involved in hepatocellular carcinoma (HCC). However, the underlying mechanism of tumorigenesis is still largely unclear. Here, we found that NEAT1 is remarkably upregulated in HCC tissues and cell lines. Overexpression of NEAT1 notably accelerated HCC cell proliferation, migration, and invasion. Knockdown of NEAT1 significantly inhibited HCC cell proliferation, migration and invasion. MiR‐384 expression was lower in HCC tissues and cell lines than adjacent nontumor tissues and L02 cell. MiR‐384 exhibited the functions of tumor‐suppressive. The expression of miR‐384 was negatively correlated with the expression of NEAT1. Overexpression of NEAT1 reduced miR‐384 expression, whereas inhibition of miR‐384 led to a distinct upregulation of NEAT1 expression. In addition, we provided evidence that miR‐384 was directly bound to the sequence of NEAT1 by luciferase reporter and RNA‐binding protein immunoprecipitation assays. Overexpression of miR‐384 inhibited NEAT1 function. Thus, we demonstrated that NEAT1 promotes the malignant biological properties of hepatocellular carcinoma by negatively regulating miR‐384.

Highlights

Hepatocellular carcinoma (HCC) is one of most common cancers worldwide and lists as the third leading cause of Liying Zhu and Nenghong Yang have contributed to this study.cancer‐related deaths around the world
We demonstrated that overexpression of nuclear‐enriched abundant transcript 1 (NEAT1) upregulated the cell proliferation– related protein Cyclin D1, the cell migration and invasion– related protein MMP2 and MMP9 expression, whereas knockdown of NEAT1 downregulated Cyclin D1, MMP2, and MMP9 expression in SMMC7721 and HepG2 cell lines (Figure 2E,F). These results suggested that NEAT1 promoted cell proliferation, migration, and invasion of hepatocellular carcinoma (HCC) and exhibited an oncogenic property in HCC tumorigenesis
LncRNA NEAT1 promotes proliferation and invasion via targeting miR‐181a‐5p in non‐small cell lung cancer.[15] Long non‐coding RNAs (lncRNAs) NEAT1 overexpression is associated with unfavorable prognosis in patients with hepatocellular carcinoma after hepatectomy, accoring to a Chinese population‐based study.[16]

Summary

| INTRODUCTION

Hepatocellular carcinoma (HCC) is one of most common cancers worldwide and lists as the third leading cause of Liying Zhu and Nenghong Yang have contributed to this study. The process of HCC involves complicated steps. Studying the pathogenesis of HCC is important. Long non‐coding RNAs (lncRNAs) are non–protein coding transcripts and longer than 200 nt.[1,2]. Emerging reports have shown that numerous lncRNAs. and microRNAs (miRNAs) are involved in multiple pathological steps of HCC, including cell proliferation, angiogenesis, cellular signaling, and metastasis.[3,4]. The LncRNA CRNDE promotes hepatic carcinoma cell proliferation, migration, and invasion by suppressing miR‐384.5 The LncRNA MEG3 inhibits cellular proliferation via negative modulation of miRNA‐664 in hepatocellular carcinoma.[6]. MALAT1, H19, HULC, and HOTAIR have been found to act as oncogenes or tumor suppressors.[7-9]

| MATERIALS AND METHODS

| RESULTS

| DISCUSSION