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Regulation of Wnt/beta‐catenin pathway by MicroRNA‐26a1
Author(s) -
Zhang Jiqiang,
Han Chang,
Wu Tong
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.442.6
The functions of miRNAs have been widely investigated under the physiological and pathological conditions. Among them, the role of MiR‐26a in cholangioncarcinoma remains unknown. In this study we showed that forced overexpression of miR‐26a1 in human cholangiocarcinoma cells (CCLP1 and SG231) promoted tumor cell growth and increased clonogenic formation capacity in vitro. Conversely, miR‐26a inhibitor inhibited tumor cell growth and prevented colonigenic formation in CCLP1 and SG231. In SCID mouse tumor xenograft model, miR‐26a1 overexpressed CCLP1 cells were found to develop larger tumor nodules than the control cells (0.37 ± 0.09 gram vs. 0.12 ± 0.02 gram) with more mitosis in miR‐26a1 overexpressing xenograft tumor tissues. We also found that glycogen synthase kinase 3 beta (GSK‐3‐beta) mRNA is the bona fide target of miR‐26a1 in cholangiocarcinoma cell lines by qRT‐PCR and Western blot. GSK‐3‐beta mRNA and miR26a1 levels were reversely correlated in these cholangiocarcinoma cell lines and forced oveexpression of miR26a1 significantly decreased GSK‐3‐beta 3′‐UTR luciferase report activity. MiR‐26a1 increased beta‐catenin activity by 2 folds with Tcf/Lef report plasmid analysis, DNA pull‐down and co‐IP experiments and miR‐26a1‐induced CCLP1 cells proliferation was blocked by beta‐catenin siRNA. Taken together, our data suggest that miRNA 26a1 enhances cholangiocarcinoma cell growth and this effect is involved in the beta‐catenin activation mediated by miR26a1‐induced GSK‐3‐beta degradation.