Long non-coding RNA SNAI3-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma by regulating the UPF1/Smad7 signalling pathway.

Yarui Li,Yan Zhao,Shuixiang He,Dan Guo,Xin Wang,Guifang Lu,Mudan Ren,Yifei Chen,Yaping Liu

doi:10.1111/jcmm.14513

Abstract

Emerging evidence has indicated that deregulation of long non‐coding RNAs (lncRNAs) can contribute to the progression of human cancers, including hepatocellular carcinoma (HCC). However, the role and exact mechanism of most lncRNAs in tumours remains largely unknown. In the current study, we found a novel long non‐coding RNA termed SNAI3‐AS1 which was generally up‐regulated in HCC tissues compared with normal control. Higher expression of SNAI3‐AS1 was significantly correlated with shorter overall survival of HCC patients. Knockdown of SNAI3‐AS1 inhibited the proliferation and metastasis of HCC cells in vitro, whereas overexpression of SNAI3‐AS1 promoted the proliferation and metastasis of HCC cells. Further investigations showed that SNAI3‐AS1 could affect HCC tumorigenesis by binding up‐frameshift protein 1 (UPF1), regulating Smad7 expression and activating TGF‐β/Smad pathway. Functionally, SNAI3‐AS1 promoted HCC growth and metastasis by inducing tumour epithelial to mesenchymal transition (EMT). Taken together, these findings showed that SNAI3‐AS1 promotes the progression of HCC by regulating the UPF1 and activating TGF‐β/Smad pathway.

Highlights

Hepatocellular carcinoma (HCC) is the dominant histological type of primary malignancies in liver and the second highest leading cause of cancer‐related death worldwide.[1]
We identified a novel HCC related Long non‐coding RNAs (lncRNAs), termed SNAI3 antisense RNA 1 (SNAI3‐AS1) by two human HCC microar‐ ray results (GSE58043 and GSE55191), and subsequently exam‐ ined the role of SNAI3‐AS1 in HCC and the potential mechanisms involved by a retrospective analysis of 46 HCC patients, and by carrying out in vitro experiments to clarify the contribution of SNAI3‐AS1 to the proliferation and metastasis of HCC and its ef‐ fect on epithelial to mesenchymal transition (EMT)
To fur‐ ther study the relationship between up‐frameshift protein 1 (UPF1) and Smad[7], two specific small interfering RNA (siRNA) against UPF1 gene transcript were introduced into HepG2 and Hep3B cells, and produced the greatest reduction

Summary

| INTRODUCTION

Hepatocellular carcinoma (HCC) is the dominant histological type of primary malignancies in liver and the second highest leading cause of cancer‐related death worldwide.[1]. The number of lncRNAs has been found to be aberrantly expressed in multiple human cancers, in‐ cluding HCC.[10-14]. These aberrant expressed lncRNAs regulate a wide range of important pathophysiological processes which as‐ sociated with tumorigenesis, metastasis, prognosis. We identified a novel HCC related lncRNA, termed SNAI3 antisense RNA 1 (SNAI3‐AS1) by two human HCC microar‐ ray results (GSE58043 and GSE55191), and subsequently exam‐ ined the role of SNAI3‐AS1 in HCC and the potential mechanisms involved by a retrospective analysis of 46 HCC patients, and by carrying out in vitro experiments to clarify the contribution of SNAI3‐AS1 to the proliferation and metastasis of HCC and its ef‐ fect on EMT

| MATERIALS AND METHODS

Findings

| DISCUSSION

| CONCLUSION