N‐myc downstream‐regulated gene 2 inhibits human cholangiocarcinoma progression and is regulated by leukemia inhibitory factor/MicroRNA‐181c negative feedback pathway

摘要: Increasing evidence supports a role for N-myc downstream-regulated gene 2 (NDRG2) deregulation in tumorigenesis. We investigated the roles and mechanisms of NDRG2 human cholangiocarcinoma (CCA) progression. In present study, expression NDRG2, microRNA (miR)-181c leukemia inhibitory factor (LIF) CCA adjacent nontumor tissues were examined. The effects on tumor growth metastasis determined both vivo vitro. NDRG2/LIF/miR-181c signaling pathway cholangiocarcinogenesis results showed that exhibited decreased levels increased miR-181c LIF compared with tissues. could inhibit cell proliferation, chemoresistance, vitro vivo. found is target miR-181c, down-regulation was attributed to overexpression CCA. Furthermore, can be activated by treatment, whereas transcription through disrupting binding between Smad, small mothers against decapentaplegic complex promoter. Down-regulation or are significantly associated poorer overall survival (OS) patients. Finally, we combination strong predictor prognosis Conclusion: These establish counteraction LIF/miR-181c as key mechanism regulates metastasis. Our elucidated novel NDRG2-mediated inhibition suggest new therapeutic targets, including LIF, transforming beta, prevention treatment. (Hepatology 2016;64:1606-1622)