LncRNA HULC regulates hepatocellular carcinoma cell proliferation, apoptosis and epithelial-mesenchymal transition via the miR-372/CXCR4 axis

Abstract

Background: Hepatocellular carcinoma (HCC) is a lethal malignancy and a major public health concern worldwide. Considering the public health risk posed by HCC, it is necessary to elucidate the mechanisms underlying liver cancer progression in order to identify more therapeutic targets. In this study, we will elucidate the role of LncRNA HULC in regulating HCC cell proliferation, apoptosis and epithelial-mesenchymal transition (EMT) via the miR-372/CXCR4 axis. Material and Methods: Target genes were predicted using the online TargetScan database. Cell models of gene over-expression and silencing were established by transfection, and the mRNA and protein expression levels were measured by qRT-PCR and Western blotting, respectively. Cell viability, proliferation and apoptosis were measured by the CCK-8 assay, colony formation assay and Annexin V-FITC/PI staining, respectively. In situ protein expression in tissues was examined by immunohistochemical staining. Results: HULC and CXCR4 were upregulated and miR-372 was downregulated in HCC tissue and cells. TargetScan prediction and dual luciferase assay revealed that miR-372 can target HULC or CXCR4. Furthermore, HULC and CXCR4 enhanced the viability of HCC cells, whereas miR-372 had the opposite effect. Consistent with this, HULC and CXCR4 increased the proliferation of these cells and miR-372 showed an inhibitory effect. Furthermore, HULC and CXCR4 blocked apoptosis in liver cancer cells and miR-372 facilitated the same. Finally, HULC and CXCR4 promoted EMT, as indicated by E-cadherin downregulation and Vimentin upregulation, whereas miR-372 had the opposite effects. Conclusion: HULC upregulates CXCR4 in HCC cells by inhibiting miR-372, which in turn promotes the proliferation, inhibits the apoptosis and accelerates the EMT of HCC cells.