Long non-coding RNA CARLo-5 promotes tumor progression in hepatocellular carcinoma via suppressing miR-200b expression
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Chunqing Dou1, Liyuan Sun1, Xin Jin1, Mingming Han1, Bao Zhang1, Xian Jiang1, Jinyong Lv1 and Tao Li1
1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China
Chunqing Dou, email: [email protected]
Keywords: hepatocellular carcinoma, CARLo-5, EZH2, miR-200b, epithelial-mesenchymal transition
Received: March 10, 2017 Accepted: June 19, 2017 Published: July 26, 2017
Long non-coding RNAs (lncRNAs) play key roles in cancer initiation and progression. The aim was to investigate the biological functions and clinical significance of long non-coding RNA CARLo-5 in hepatocellular carcinoma (HCC). QRT-PCR was performed to investigate CARLo-5 expression in HCC tissues and cells. Kaplan-Meier curve and multivariate analysis validated the association between CARLo-5 expression and overall survival (OS) in HCC patients. Cell proliferation and invasion was performed by CCK8 cell proliferation, cell colony formation and transwell invasion assays. Western-blot assay was performed to evaluate the protein expression of Twist1, ZEB1, E-cadherin and Vimentin. Tumor xenografts were performed to evaluate the effect of CARLo-5 on tumor growth in vivo. RNA Immunoprecipitation (RIP) and Chromatin Immunoprecipitation (ChIP) were also performed. Our results showed that CARLo-5 expression was significantly higher in HCC tissues and upregulated CARLo-5 expression was closely correlated with tumor size and advanced tumor stage. Kaplan-Meier curve and multivariate analysis validated that higher CARLo-5 expression predicted a poor prognosis for HCC patients and was an independent risk factor for OS in HCC patients. In vitro, knockdown of CARLo-5 inhibited cell proliferation, colony formation, cell invasion and inhibited the cell epithelial-mesenchymal transition (EMT) by up-regulating the E-cadherin expression and down-regulating Twist1, ZEB1 and vimentin expression in HCC cells. Furthermore, we demonstrated that CARLo-5 inhibited the miR-200b expression via EZH2. In vivo, knockdown of CARLo-5 significantly inhibited the tumor growth. Thus, our results indicated that CARLo-5 represented a novel tumor biomarker and therapeutic target for HCC.
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