Downregulation of miR-610 promotes proliferation and tumorigenicity and activates Wnt/β-catenin signaling in human hepatocellular carcinoma

Molecular Cancer

Research

Fo-Qiu Liu¹  Rong Yan¹  Xian-Cheng Zeng²  Guo-Ying Wang³  Yang Li³  Tong Zhang³  Hui-Min Yi³  Nan Jiang³ 

[1] Department of Gastroenterology, Zengcheng People’s Hospital (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng, Guangdong, China;Department of General Surgery, Zengcheng People’s Hospital, (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng, Guangdong, China;Department of clinical laboratory, Zengcheng People’s Hospital (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng, Guangdong, China;Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Road, Tian He District, 310630, Guangzhou, Guangdong, China;Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Road, Tian He District, 310630, Guangzhou, Guangdong, China;

关键词: HCC;    miR-610;    Proliferation;    Wnt/β-catenin;    LRP6;    TBL1X;   

DOI  :  10.1186/1476-4598-13-261

 received in 2014-07-22, accepted in 2014-11-13,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundWnt/β-catenin signaling pathway plays important roles in human cancer progression. Better understanding the mechanism underlying regulation of Wnt/β-catenin signaling pathway might provide novel therapeutic targets for cancer treatment.MethodsmiR-610 expression levels in hepatocellular carcinoma (HCC) cell lines, HCC tissues and 76 archived HCC specimens were determined using real-time PCR. Cell viability was measured by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. The level of DNA synthesis was determined by BrdU incorporation assay. Flow cytometry analysis was used to analyze cell cycle progression. The cells proliferation and tumorigenesis were determined by colony formation and anchorage-independent growth assays in vitro, and by xenograft tumors in vivo. Luciferase assay and micro-ribonucleoprotein complex immunoprecipitation assay were used to confirm the association of the targeted mRNAs with miR-610.ResultsmiR-610 was downregulated in human HCC cells and tissues, and correlated with HCC progression and patient survival. Inhibition of miR-610 promoted, but overexpression of miR-610 reduced, HCC cell proliferation and tumorigenicity both in vitro and in vivo. Furthermore, we found that inhibiting miR-610 activated, but overexpressing miR-610 decreased, the Wnt/β-catenin activity through directly suppressing lipoprotein receptor-related protein 6 (LRP6) and transducin β–like protein 1 (TBL1X). The in vitro analysis was consistent with the inverse correlation detected between miR-610 levels with expression of LRP6 and TBL1X in a cohort of human HCC samples.ConclusionsOur results indicate that miR-610 downregulation plays essential roles in HCC progression and reduced miR-610 is correlated with Wnt/β-catenin signaling pathway.

【 授权许可】

Unknown   
© Zeng et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.