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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).
DescriptionLink to Free access
Persistent Identifierhttp://hdl.handle.net/10722/236984
ISSN
2023 Impact Factor: 12.9
2023 SCImago Journal Rankings: 5.011
ISI Accession Number ID
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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.descriptionLink to Free access-
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.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.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/hep.28821-
dc.identifier.pmid27639189-
dc.identifier.scopuseid_2-s2.0-84995700052-
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-
dc.relation.projectA Multidisciplinary Study on CD133 Liver Cancer Stem Cells: Molecular Mechanisms, Clinical Relevance and Therapeutic Implications-
dc.identifier.issnl0270-9139-

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