Dataset Information

MiR-26a induced the suppression of tumor growth of cholangiocarcinoma via KRT19 approach.

ABSTRACT:

Background and aims

KRT19 was identified as one of the key biomarkers for distinguishing cholangiocarcinoma (CCA) and hepatocellular carcinoma. The detailed role of miRNAs involved in the oncogenic incident of KRT19 was poor investigated.

Results

Based on prediction and validation, miR-26a was inversely correlated with KRT19 in patients' tissues samples and biopsies. Ectopic expression of miR-26a dramatically suppressed cell proliferation and tumor growth in vitro and in vivo. Knock-down miR-26a could induce an increasing population of SP cells by promoting KRT19 expression. The KRT19 was also suppressed via directly binding at 3'UTR region by miR-26a.

Materials and methods

Bioinformatics prediction was first applied to screening the potential miRNA involved. RT-PCR, Immunohistochemistry and Western blot were used to examine the expression of miRNAs and candidate genes in 65 pairs of cholangiocarcinoma. The loss-and gain-function assay was employed to detect the role of certain miRNA in vitro and vivo. Side-population (SP) cells were detected and sorted by flow cytometry.

Conclusions

Aberrant decreased miR-26a could promote cell proliferation by regulating KRT19 which play important roles in the pathogenesis of CCA.

SUBMITTER: Wang P

PROVIDER: S-EPMC5348398 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Publications

miR-26a induced the suppression of tumor growth of cholangiocarcinoma via KRT19 approach.

Wang Ping P Lv Long L

Oncotarget 20161201 49

<h4>Background and aims</h4>KRT19 was identified as one of the key biomarkers for distinguishing cholangiocarcinoma (CCA) and hepatocellular carcinoma. The detailed role of miRNAs involved in the oncogenic incident of KRT19 was poor investigated.<h4>Results</h4>Based on prediction and validation, miR-26a was inversely correlated with KRT19 in patients' tissues samples and biopsies. Ectopic expression of miR-26a dramatically suppressed cell proliferation and tumor growth in vitro and in vivo. Kno ...[more]

PMID: 27833076

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Project description:Background & aimsMicroRNAs (miRNAs) have been implicated in the development and progression of human cancers. We investigated the roles and mechanisms of miR-26a in human cholangiocarcinoma.MethodsWe used in situ hybridization and quantitative reverse transcriptase polymerase chain reaction to measure expression of miR-26a in human cholangiocarcinoma tissues and cell lines (eg, CCLP1, SG231, HuCCT1, TFK1). Human cholangiocarcinoma cell lines were transduced with lentiviruses that expressed miR-26a1 or a scrambled sequence (control); proliferation and colony formation were analyzed. We analyzed growth of human cholangiocarcinoma cells that overexpress miR-26a or its inhibitor in severe combined immune-deficient mice. Immunoblot, immunoprecipitation, DNA pull-down, immunofluorescence, and luciferase reporter assays were used to measure expression and activity of glycogen synthase kinase (GSK)-3β, β-catenin, and related signaling molecules.ResultsHuman cholangiocarcinoma tissues and cell lines had increased levels of miR-26a compared with the noncancerous biliary epithelial cells. Overexpression of miR-26a increased proliferation of cholangiocarcinoma cells and colony formation in vitro, whereas miR-26 depletion reduced these parameters. In severe combined immune-deficient mice, overexpression of miR-26a by cholangiocarcinoma cells increased tumor growth and overexpression of the miR-26a inhibitor reduced it. GSK-3β messenger RNA was identified as a direct target of miR-26a by computational analysis and experimental assays. miR-26a-mediated reduction of GSK-3β resulted in activation of β-catenin and induction of several downstream genes including c-Myc, cyclinD1, and peroxisome proliferator-activated receptor δ. Depletion of β-catenin partially prevented miR-26a-induced tumor cell proliferation and colony formation.ConclusionsmiR-26a promotes cholangiocarcinoma growth by inhibition of GSK-3β and subsequent activation of β-catenin. These signaling molecules might be targets for prevention or treatment of cholangiocarcinoma.