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Title: Interaction of lncRNA-MALAT1 and miR-124 regulates HBx-induced cancer stem cell properties in HepG2 through PI3K/Akt signaling. Author: He B, Peng F, Li W, Jiang Y. Journal: J Cell Biochem; 2019 Mar; 120(3):2908-2918. PubMed ID: 30500989. Abstract: BACKGROUND: Hepatitis B virus X protein (HBx) plays a crucial role in initiating and promoting HBV-induced hepatocellular carcinoma (HCC) development. Reports indicated that HBx promotes cancer stem cell (CSC) generation, which may be associated with HBV-related HCC. Noncoding RNA miR-124 and long noncoding RNA (lncRNA)-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) were considered to be involved deeply in the progress of HBx-related HCC. Hence, the underlying mechanism of miR-124 and lncRNA-MALAT1 in regulating HBx-promoted CSC needs to be studied. MATERIALS AND METHODS: In present study, HepG2-X cell line was induced by transfect HBx into HepG2 cells. Overexpressing of miR-124 or silencing of lncRNA-MALAT1 was completed by transfecting miR-124 mimic or shMALAT1 into HepG2-X cells. HBx-induced CSC properties and tumorigenic potential of HepG2 cells were determined by detecting CSC marker expression, colony formation assay, and xenograft tumorigenesis. The mechanism of HBx-induced CSC properties was explored by PI3K/Akt inhibitor. Interaction of miR-124 and lncRNA-MALAT1 was detected by luciferase reporter assay. RESULTS: HBx promoted CSC properties through upregulating stemness markers and reprogramming proteins, and contributed to tumorigenicity of HepG2-X cells both in vivo and in vitro. Inhibition of Akt activation blocked the HBx-stimulated reprogramming proteins and stemness markers. HBx upregulated lncRNA-MALAT1 expression while downregulating miR-124 expression in HepG2-X cells. miR-124 interacts with lncRNA-MALAT1 by direct targeting. Overexpression of miR-124 or silencing of lncRNA-MALAT1 both blocked HBx-induced CSC generation, stemness-related factor activation and tumorigenicity via PI3K/Akt signaling. CONCLUSION: Our results demonstrated that miR-124 interact with lncRNA-MALAT1 and involve in regulating HBx-induced CSC properties via PI3K/Akt signaling.[Abstract] [Full Text] [Related] [New Search]