Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/65506
Title: Octamer 4/microRNA-1246 signaling axis drives Wnt/β-catenin activation in liver cancer stem cells
Authors: Chai, S
Ng, KY
Tong, M
Lau, EY
Lee, TK 
Chan, KW
Yuan, YF
Cheung, TT
Cheung, ST
Wang, XQ
Wong, N
Lo, CM
Man, K
Guan, XY
Ma, S
Issue Date: 2016
Publisher: Wiley
Source: Hepatology, 2016, v. 64, no. 6, p. 2062-2076 How to cite?
Journal: Hepatology 
Abstract: Wnt/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. Conclusion: These findings uncover the noncanonical regulation of Wnt/β-catenin in liver CSCs by the Oct4/miR-1246 signaling axis, and also provide a novel diagnostic marker as well as therapeutic intervention for HCC. (Hepatology 2016;64:2062-2076).
URI: http://hdl.handle.net/10397/65506
ISSN: 0270-9139
EISSN: 1527-3350
DOI: 10.1002/hep.28821
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