Downregulation of miR-610 promotes proliferation and tumorigenicity and activates Wnt-β-catenin signaling in human hepatocellular carcinomaReport as inadecuate




Downregulation of miR-610 promotes proliferation and tumorigenicity and activates Wnt-β-catenin signaling in human hepatocellular carcinoma - Download this document for free, or read online. Document in PDF available to download.

Molecular Cancer

, 13:261

First Online: 10 December 2014Received: 22 July 2014Accepted: 13 November 2014DOI: 10.1186-1476-4598-13-261

Cite this article as: Zeng, XC., Liu, FQ., Yan, R. et al. Mol Cancer 2014 13: 261. doi:10.1186-1476-4598-13-261

Abstract

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.

KeywordsHCC miR-610 Proliferation Wnt-β-catenin LRP6 TBL1X AbbreviationsLRP6Lipoprotein receptor-related protein 6

TBL1XTransducin β–like protein 1

HCCHepatocellular carcinoma

miRNA or miRmicroRNAs

3′UTR3′untranslated region

NF-κBNuclear factor κB

BrdU5-bromo-2′-deoxyuridine-5′-monophosphate

MTT3-4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-13-261 contains supplementary material, which is available to authorized users.

Xian-Cheng Zeng, Fo-Qiu Liu, Rong Yan contributed equally to this work.

Download fulltext PDF



Author: Xian-Cheng Zeng - Fo-Qiu Liu - Rong Yan - Hui-Min Yi - Tong Zhang - Guo-Ying Wang - Yang Li - Nan Jiang

Source: https://link.springer.com/







Related documents