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Article: PRMT6 Regulates RAS/RAF Binding and MEK/ERK-Mediated Cancer Stemness Activities in Hepatocellular Carcinoma through CRAF Methylation

TitlePRMT6 Regulates RAS/RAF Binding and MEK/ERK-Mediated Cancer Stemness Activities in Hepatocellular Carcinoma through CRAF Methylation
Authors
KeywordsArginine methylation
Cancer stemness
Epigenetics
HCC
Tumor-initiating cells
Issue Date2018
PublisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports
Citation
Cell Reports, 2018, v. 25 n. 3, p. 690-701.e8 How to Cite?
AbstractArginine methylation is a post-translational modification that plays pivotal roles in signal transduction and gene transcription during cell fate determination. We found protein methyltransferase 6 (PRMT6) to be frequently downregulated in hepatocellular carcinoma (HCC) and its expression to negatively correlate with aggressive cancer features in HCC patients. Silencing of PRMT6 promoted the tumor-initiating, metastasis, and therapy resistance potential of HCC cell lines and patient-derived organoids. Consistently, loss of PRMT6 expression aggravated liver tumorigenesis in a chemical-induced HCC PRMT6 knockout (PRMT6−/−) mouse model. Integrated transcriptome and protein-protein interaction studies revealed an enrichment of genes implicated in RAS signaling and showed that PRMT6 interacted with CRAF on arginine 100, which decreased its RAS binding potential and altered its downstream MEK/ERK signaling. Our work describes a critical repressive function for PRMT6 in maintenance of HCC cells by regulating RAS binding and MEK/ERK signaling via methylation of CRAF on arginine 100.
Persistent Identifierhttp://hdl.handle.net/10722/261083
ISSN
2023 Impact Factor: 7.5
2023 SCImago Journal Rankings: 4.279
ISI Accession Number ID
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DC FieldValueLanguage
dc.contributor.authorChan, LH-
dc.contributor.authorZhou, L-
dc.contributor.authorNg, KY-
dc.contributor.authorWong, TL-
dc.contributor.authorLee, TK-
dc.contributor.authorSharma, R-
dc.contributor.authorLoong, HC-
dc.contributor.authorChing, YP-
dc.contributor.authorYuan, YF-
dc.contributor.authorXie, D-
dc.contributor.authorLo, CM-
dc.contributor.authorMan, K-
dc.contributor.authorArtegiani, B-
dc.contributor.authorClevers, H-
dc.contributor.authorYan, HHN-
dc.contributor.authorLeung, SY-
dc.contributor.authorRichard, S-
dc.contributor.authorGuan, X-
dc.contributor.authorHuen, MSY-
dc.contributor.authorMa, SKY-
dc.date.accessioned2018-09-14T08:52:12Z-
dc.date.available2018-09-14T08:52:12Z-
dc.date.issued2018-
dc.identifier.citationCell Reports, 2018, v. 25 n. 3, p. 690-701.e8-
dc.identifier.issn2211-1247-
dc.identifier.urihttp://hdl.handle.net/10722/261083-
dc.description.abstractArginine methylation is a post-translational modification that plays pivotal roles in signal transduction and gene transcription during cell fate determination. We found protein methyltransferase 6 (PRMT6) to be frequently downregulated in hepatocellular carcinoma (HCC) and its expression to negatively correlate with aggressive cancer features in HCC patients. Silencing of PRMT6 promoted the tumor-initiating, metastasis, and therapy resistance potential of HCC cell lines and patient-derived organoids. Consistently, loss of PRMT6 expression aggravated liver tumorigenesis in a chemical-induced HCC PRMT6 knockout (PRMT6−/−) mouse model. Integrated transcriptome and protein-protein interaction studies revealed an enrichment of genes implicated in RAS signaling and showed that PRMT6 interacted with CRAF on arginine 100, which decreased its RAS binding potential and altered its downstream MEK/ERK signaling. Our work describes a critical repressive function for PRMT6 in maintenance of HCC cells by regulating RAS binding and MEK/ERK signaling via methylation of CRAF on arginine 100.-
dc.languageeng-
dc.publisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports-
dc.relation.ispartofCell Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectArginine methylation-
dc.subjectCancer stemness-
dc.subjectEpigenetics-
dc.subjectHCC-
dc.subjectTumor-initiating cells-
dc.titlePRMT6 Regulates RAS/RAF Binding and MEK/ERK-Mediated Cancer Stemness Activities in Hepatocellular Carcinoma through CRAF Methylation-
dc.typeArticle-
dc.identifier.emailZhou, L: lenazhou@connect.hku.hk-
dc.identifier.emailNg, KY: jkyng@hku.hk-
dc.identifier.emailWong, TL: tinlwong@hku.hk-
dc.identifier.emailChing, YP: ypching@hku.hk-
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hk-
dc.identifier.emailMan, K: kwanman@hku.hk-
dc.identifier.emailYan, HHN: yanhelen@hkucc.hku.hk-
dc.identifier.emailLeung, SY: suetyi@hku.hk-
dc.identifier.emailGuan, X: xyguan@hku.hk-
dc.identifier.emailHuen, MSY: huen.michael@hku.hk-
dc.identifier.emailMa, SKY: stefma@hku.hk-
dc.identifier.authorityChing, YP=rp00469-
dc.identifier.authorityLo, CM=rp00412-
dc.identifier.authorityMan, K=rp00417-
dc.identifier.authorityYan, HHN=rp01994-
dc.identifier.authorityLeung, SY=rp00359-
dc.identifier.authorityGuan, X=rp00454-
dc.identifier.authorityHuen, MSY=rp01336-
dc.identifier.authorityMa, SKY=rp00506-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.celrep.2018.09.053-
dc.identifier.pmid30332648-
dc.identifier.scopuseid_2-s2.0-85054755052-
dc.identifier.hkuros291189-
dc.identifier.hkuros294939-
dc.identifier.volume25-
dc.identifier.issue3-
dc.identifier.spage690-
dc.identifier.epage701.e8-
dc.identifier.isiWOS:000448217500014-
dc.publisher.placeUnited States-
dc.relation.projectA Multidisciplinary Study on CD133 Liver Cancer Stem Cells: Molecular Mechanisms, Clinical Relevance and Therapeutic Implications-
dc.identifier.issnl2211-1247-

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