Oct4/miR-1246 signaling axis drives Wnt/β-catenin activation in liver cancer stem cells
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AbstractWnt/β-catenin signaling is activated in CD133 liver cancer stem cells (CSCs), a subset of cells known to be a root of tumor recurrence and therapy resistance in hepatocellular carcinoma (HCC). However, the regulatory mechanism of this pathway in CSCs remains unclear. Here, we show that human microRNA (miRNA), miR-1246, promotes cancer stemness, including self-renewal, drug resistance, tumorigencity, and metastasis, by activation of the Wnt/β-catenin pathway through suppressing the expression of AXIN2 and glycogen synthase kinase 3β (GSK3β), two key members of the β-catenin destruction complex. Clinically, high endogenous and circulating miR-1246 was identified in HCC clinical samples and correlated with a worse prognosis. Further functional analysis identified octamer 4 (Oct4) to be the direct upstream regulator of miR-1246, which cooperatively drive β-catenin activation in liver CSCs.
All Author(s) ListChai S, Ng KY, Tong M, Lau EY, Lee TK, Wah Chan K, Yuan YF, Cheung TT, Cheung ST, Wang XQ, Wong N, Lo CM, Man K, Guan XY, Ma S
Journal nameHepatology
Volume Number64
Issue Number6
PublisherWiley: 12 months
Pages2062 - 2076
LanguagesEnglish-United Kingdom

Last updated on 2021-16-09 at 01:49