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Article: Octamer 4/microRNA‐1246 signaling axis drives Wnt/β‐catenin activation in liver cancer stem cells

TitleOctamer 4/microRNA‐1246 signaling axis drives Wnt/β‐catenin activation in liver cancer stem cells
Authors
Issue Date2016
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2016, v. 64 n. 6, p. 2062-2076 How to Cite?
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. 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).
Persistent Identifierhttp://hdl.handle.net/10722/236984
ISSN
2017 Impact Factor: 14.079
2015 SCImago Journal Rankings: 4.752
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChai, S-
dc.contributor.authorNg, KY-
dc.contributor.authorTong, M-
dc.contributor.authorLau, EY-
dc.contributor.authorLee, TK-
dc.contributor.authorChan, KW-
dc.contributor.authorYuan, YF-
dc.contributor.authorCheung, TT-
dc.contributor.authorCheung, ST-
dc.contributor.authorWang, X-
dc.contributor.authorWong, N-
dc.contributor.authorLo, CM-
dc.contributor.authorMan, K-
dc.contributor.authorGuan, X-
dc.contributor.authorMa, SKY-
dc.date.accessioned2016-12-20T06:14:25Z-
dc.date.available2016-12-20T06:14:25Z-
dc.date.issued2016-
dc.identifier.citationHepatology, 2016, v. 64 n. 6, p. 2062-2076-
dc.identifier.issn0270-9139-
dc.identifier.urihttp://hdl.handle.net/10722/236984-
dc.description.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. 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).-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/-
dc.relation.ispartofHepatology-
dc.rightsHepatology. Copyright © John Wiley & Sons, Inc.-
dc.rightsPreprint: This is the pre-peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Postprint: This is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Special Statement for Preprint only Before publication: 'This is a preprint of an article accepted for publication in [The Journal of Pathology] Copyright © ([year]) ([Pathological Society of Great Britain and Ireland])'. After publication: the preprint notice should be amended to follows: 'This is a preprint of an article published in [include the complete citation information for the final version of the Contribution as published in the print edition of the Journal]' For Cochrane Library/ Cochrane Database of Systematic Reviews, add statement & acknowledgement : ‘This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 20XX, Issue X. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.’ Please include reference to the Review and hyperlink to the original version using the following format e.g. Authors. Title of Review. Cochrane Database of Systematic Reviews 20XX, Issue #. Art. No.: CD00XXXX. DOI: 10.1002/14651858.CD00XXXX (insert persistent link to the article by using the URL: http://dx.doi.org/10.1002/14651858.CD00XXXX) (This statement should refer to the most recent issue of the Cochrane Database of Systematic Reviews in which the Review published.)-
dc.titleOctamer 4/microRNA‐1246 signaling axis drives Wnt/β‐catenin activation in liver cancer stem cells-
dc.typeArticle-
dc.identifier.emailChai, S: stchai@hku.hk-
dc.identifier.emailTong, M: caroltm@hku.hk-
dc.identifier.emailChan, KW: hrmtckw@hkucc.hku.hk-
dc.identifier.emailCheung, TT: cheung68@hku.hk-
dc.identifier.emailCheung, ST: stcheung@hkucc.hku.hk-
dc.identifier.emailWang, X: xqwang@hku.hk-
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hk-
dc.identifier.emailMan, K: kwanman@hku.hk-
dc.identifier.emailGuan, X: xyguan@hkucc.hku.hk-
dc.identifier.emailMa, SKY: stefma@hku.hk-
dc.identifier.authorityChan, KW=rp00330-
dc.identifier.authorityCheung, TT=rp02129-
dc.identifier.authorityCheung, ST=rp00457-
dc.identifier.authorityWang, X=rp00507-
dc.identifier.authorityLo, CM=rp00412-
dc.identifier.authorityMan, K=rp00417-
dc.identifier.authorityGuan, X=rp00454-
dc.identifier.authorityMa, SKY=rp00506-
dc.identifier.doi10.1002/hep.28821-
dc.identifier.pmid27639189-
dc.identifier.hkuros270726-
dc.identifier.hkuros262824-
dc.identifier.volume64-
dc.identifier.issue6-
dc.identifier.spage2062-
dc.identifier.epage2076-
dc.identifier.isiWOS:000393900200061-
dc.publisher.placeUnited States-

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