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

// Wuyuan Zhou 1 , Benkui Zou 2 , Lisheng Liu 3 , Kai Cui 1 , Jie Gao 1 , Shuanghu Yuan 4 , Ning Cong 5 1 Department of Hepatobillary Surgery, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China 2 Department of Urology Surgery, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China 3 Clinical Laboratory, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China 4 Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China 5 Department of Intervention Therapy, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China Correspondence to: Ning Cong, email: doctorcongning@qq.com Keywords: hepatocellular carcinoma, microRNA-98, tumor suppressor, SALL4 Received: June 22, 2016      Accepted: August 16, 2016      Published: September 22, 2016 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.