MicroRNA-33b suppresses the proliferation and metastasis of hepatocellular carcinoma cells through the inhibition of Sal-like protein 4 expression

• Published in: International journal of molecular medicine 2016-11, Vol.38 (5), p.1587-1595
• Main Authors: Tian, Qinggang, Xiao, Yao, Wu, Yanting, Liu, Yun, Song, Zhiqing, Gao, Wenfeng, Zhang, Jing, Yang, Jingling, Zhang, Yuguo, Guo, Tuankui, Dai, Furong, Sun, Zhigang
• Format: Article
• Language: English
• Subjects: Care and treatment; Cell growth; Development and progression; Gene expression; Genes; Genetic aspects; Health aspects; hepatocellular carcinoma; Hepatoma; Hospitals; invasion; Liver cancer; Metastasis; MicroRNA; microRNA-33b; migration; proliferation; Proteins; Regulation; Roles; Sal-like protein 4; Stem cells; Studies; Wound healing
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2016.2754

MicroRNAs (miRNAs or miRs) have been found to participate in the development and malignant progression of human cancers by negatively mediating the expression of their target genes. Recently, miR-33b has been reported to be involved in multiple types of human cancer, including hepatocellular carcinoma (HCC). However, the underlying regulatory mechanisms of miR-33b in HCC cell growth and metastasis remain largely unclear. In the present study, RT-qPCR revealed that miR-33b was significantly downregulated in HCC tissues compared to their matched adjacent normal tissues. Moreover, the miR-33b level was significantly lower in advanced-stage HCC (stages T3-T4) compared to early-stage HCC (stages T1-T2). Furthermore, it was also downregulated in the HCC cell lines, LH86, HepG2, LMH and PLHC-1, when compared with the THLE-3 normal human liver cells. We further demonstrated that the overexpression of miR-33b led to a significant decrease in the proliferation, migration and invasion of HepG2 and LH86 cells. Luciferase reporter assay identified Sal-like protein 4 (SALL4) as a target gene of miR-33b, and its protein expression was negatively regulated by miR-33b in HepG2 and LH86 cells. Moreover, the restoration of SALL4 expression markedly reversed the inhibitory effect of miR-33b overexpression on the proliferation, migration and invasion of HepG2 and LH86 cells, indicating that SALL4 is involved in miR-33b-mediated malignant phenotypes of HCC cells. Furthermore, we found that SALL4 was significantly upregulated in HCC tissues compared to their matched adjacent normal tissues, and its increased expression was significantly associated with the advanced malignancy of HCC. Moreover, SALL4 was also upregulated in HCC cell lines compared to the THLE-3 normal human liver cells. Finally, we found that the SALL4 expression inversely correlated with the miR-33b level in HCC tissues. On the whole, the findings of our study demonstrate that miR-33b suppresses the proliferation and metastasis of HCC cells through the inhibition of SALL4 expression. Therefore, miR-33b/SALL4 may become a potential therapeutic target for the treatment of HCC.