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  • Title: XIST Induced by JPX Suppresses Hepatocellular Carcinoma by Sponging miR-155-5p.
    Author: Lin XQ, Huang ZM, Chen X, Wu F, Wu W.
    Journal: Yonsei Med J; 2018 Sep; 59(7):816-826. PubMed ID: 30091314.
    Abstract:
    PURPOSE: The influence of X-inactive specific transcript (XIST) and X-chromosome inactivation associated long non-coding RNAs (lncRNAs) just proximal to XIST (JPX) on hepatocellular carcinoma (HCC) remains controversial in light of previous reports, which the present study aimed to verify. MATERIALS AND METHODS: The DIANA lncRNA-microRNA (miRNA) interaction database was used to explore miRNA interactions with JPX or XIST. JPX, XIST, and miR-155-5p expression levels in paired HCC specimens and adjacent normal tissue were analyzed by RT-qPCR. Interaction between XIST and miR-155-5p was verified by dual luciferase reporter assay. Expression levels of miR-155-5p and its known target genes, SOX6 and PTEN, were verified by RT-qPCR and Western blot in HepG2 cells with or without XIST knock-in. The potential suppressive role of XIST and JPX on HCC was verified by cell functional assays and tumor formation assay using a xenograft model. RESULTS: JPX and XIST expression was significantly decreased in HCC pathologic specimens, compared to adjacent tissue, which correlated with HCC progression and increased miR-155-5p expression. Dual luciferase reporter assay revealed XIST as a direct target of miR-155-5p. XIST knock-in significantly reduced miR-155-5p expression level and increased that of SOX6 and PTEN, while significantly inhibiting HepG2 cell growth in vitro, which was partially reversed by miR-155-5p mimic transfection. JPX knock-in significantly increased XIST expression and inhibited HepG2 cell growth in vitro or tumor formation in vivo in a XIST dependent manner. CONCLUSION: JPX and XIST play a suppressive role in HCC. JPX increases expression levels of XIST in HCC cells, which suppresses HCC development by sponging the cancer promoting miR-155-5p.
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