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

Abstract

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.

Up-regulated microRNA-33b inhibits epithelial–mesenchymal transition in gallbladder cancer through down-regulating CROCC

“…Our study also demonstrated that miR-33b could suppress various cellular processes such as invasion, migration, proliferation, EMT, and tumor growth of GBC through down-regulating the expression of CROCC. In consistency with our study, Wu et al also observed that the overexpression of miR-33b suppressed the proliferation, migration, and invasion of hepatocellular carcinoma cells [30]. Also, an enforced expression of miR-33b resulted in its inhibitory effects on EMT in lung cancer cells [31].…”

Construction and Prognostic Analysis of miRNA-mRNA Regulatory Network in Liver Metastasis from Colorectal Cancer

“…[42] hsa-miR-33b-5p was shown to constrain tumor cell growth and induce cell cycle arrest, and decreased expression level in liver cancer and CRC, which is inconformity with the results of this paper. [43,44] However, there is a study that show high expression of miR-33b in lung cancer. [45] SLCO1B3 gene encodes organic anion transporting polypeptide 1B3 (OATP1B3).…”

Long noncoding RNA Z38 promotes cell proliferation and metastasis and inhibits cell apoptosis in human gastric cancer

“…In China, gastric cancer is the third most common cause of cancer-associated mortality ( 18 ). In the year 2002, the age standardized incidence rate was 22.0/100,000 males and 10.4/100,000 females and the mortality rate was 16.3/100,000 males and 7.9/100,000 females, according to the global estimation-GLOBOCAN 2002 ( 19 ). The property of easy distant metastasis makes current therapeutics unable to treat gastric cancer in all patients.…”