MicroRNA-98 acts as a tumor suppressor in hepatocellular carcinoma via targeting SALL4.

Wuyuan Zhou,Jie Gao,Kai Cui,Ning Cong,Shuanghu Yuan,Lisheng Liu,Benkui Zou

doi:10.18632/oncotarget.12190

Abstract

MicroRNAs (miRs) are involved in the development and progression of hepatocellular carcinoma (HCC), but the regulatory mechanism of miR-98 in HCC still remains unclear. Here we found that miR-98 was significantly downregulated in HCC tissues compared to matched adjacent normal tissues (ANTs). Low miR-98 expression was associated with tumor size, metastasis, portal vein tumor embolus, and poor overall survival. Ectopic expression of miR-98 decreased the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells. SALL4 was identified as a novel target of miR-98, and the protein expression of SALL4 was inhibited by miR-98 in HCC cells. Overexpression of SALL4 reversed the suppressive effects of miR-98 on the malignant phenotypes of HCC cells. Besides, SALL4, upregulated in HCC tissues compared to the matched ANTs, was inversely correlated to the miR-98 levels in HCC tissues. In addition, overexpression of miR-98 markedly suppressed the tumor growth as well as tumor-induced death in nude mice. In summary, miR-98 plays a suppressive role in the proliferation, migration, invasion and EMT of HCC cells, partly at least, via directly inhibition of SALL4. Therefore, the miR-98/SALL4 axis may become a promising therapeutic target for HCC.

Highlights

Hepatocellular carcinoma (HCC), one of the most common cancers in human, causes 1 million deaths a year, and is one of the leading causes of cancerrelated death worldwide [1, 2]
These findings suggest that downregulation of miR-98 may contribute to the malignant progression of hepatocellular carcinoma (HCC)
Real-time RT-PCR data indicated that Sal-like protein 4 (SALL4) was upregulated in HCC tissues compared to adjacent normal tissues (ANTs) (Figure 9A)

Summary

Introduction

Hepatocellular carcinoma (HCC), one of the most common cancers in human, causes 1 million deaths a year, and is one of the leading causes of cancerrelated death worldwide [1, 2]. Understanding of the molecular mechanisms underlying HCC is important for the development of effective treatment strategies, and deregulations of oncogenes or tumor suppressors have been demonstrated to be involved in the development and progression of HCC [3, 4]. Deregulations of miRs are implicated in the development and malignant progression of human cancers via inhibition of their targets that are oncogenes or tumor suppressors [9, 10]. Deregulations of many miRs have been implicated in the growth and metastasis of HCC, such as miR-21 [11], miR-101 [12], miR-124 [13], miR-203 [13], and miR-148 [14], which may be used as potential therapeutic targets or candidates for HCC treatment

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