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Article: Epigenetic silencing of EVL/miR-342 in multiple myeloma

TitleEpigenetic silencing of EVL/miR-342 in multiple myeloma
Authors
Issue Date2018
PublisherMosby, Inc. The Journal's web site is located at https://www.journals.elsevier.com/translational-research
Citation
Translational Research, 2018, v. 192, p. 46-53 How to Cite?
AbstractmiR-342-3p, localized to 14q32, is a tumor suppressor miRNA implicated in multiple cancers. As the promoter region of its host gene, EVL, is embedded in a CpG island, we postulated that miR-342-3p is an intronic miRNA co-regulated with its host gene by promoter DNA methylation in multiple myeloma (MM). By methylation-specific polymerase chain reaction, verified by quantitative bisulfite pyrosequencing, methylation of EVL/miR-342 was absent in all healthy controls (n = 10) and 12 of 15 (80%) human myeloma cell lines (HMCLs), but partially methylated in 3 of 15 (20%) HMCLs, including KMS-12-PE, OCI-MY5, and RPMI-8226R. In HMCLs, by real-time quantitative reverse transcription-polymerase chain reaction, methylation of EVL/miR-342 correlated with lower expression of both EVL (P = 0.013) and miR-342-3p (P = 0.023). Moreover, in KMS-12-PE and RPMI-8226R cells, both partially methylated for EVL/miR-342, 5-AzadC treatment led to demethylation of EVL/miR-342 and re-expression of miR-342-3p. Upon removal of 5-AzadC, continuous culture resulted in restoration of EVL/miR-342 methylation and downregulation of miR-342-3p. In primary samples, methylation of EVL/miR-342 was detected in 1 of 18 (5.6%) monoclonal gammopathy of undetermined significance (MGUS), 8 of 63 (12.7%) diagnostic MM, and 5 of 30 (16.7%) relapsed MM. EVL/miR-342 methylation was preferentially detected in IgD MM but not found to impact survival. Collectively, in MM, miR-342-3p is an intronic miRNA regulated by promoter DNA methylation of its host gene, EVL, in a tumor-specific manner. Methylation of EVL/miR-342 was present in consecutive stages of myelomagenesis including MGUS, diagnostic MM, and relapsed MM.
Persistent Identifierhttp://hdl.handle.net/10722/271993
ISSN
2019 Impact Factor: 5.411
2015 SCImago Journal Rankings: 1.812
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, Z-
dc.contributor.authorWong, KY-
dc.contributor.authorChan, GCF-
dc.contributor.authorChng, WJ-
dc.contributor.authorChim, CS-
dc.date.accessioned2019-07-20T10:33:35Z-
dc.date.available2019-07-20T10:33:35Z-
dc.date.issued2018-
dc.identifier.citationTranslational Research, 2018, v. 192, p. 46-53-
dc.identifier.issn1931-5244-
dc.identifier.urihttp://hdl.handle.net/10722/271993-
dc.description.abstractmiR-342-3p, localized to 14q32, is a tumor suppressor miRNA implicated in multiple cancers. As the promoter region of its host gene, EVL, is embedded in a CpG island, we postulated that miR-342-3p is an intronic miRNA co-regulated with its host gene by promoter DNA methylation in multiple myeloma (MM). By methylation-specific polymerase chain reaction, verified by quantitative bisulfite pyrosequencing, methylation of EVL/miR-342 was absent in all healthy controls (n = 10) and 12 of 15 (80%) human myeloma cell lines (HMCLs), but partially methylated in 3 of 15 (20%) HMCLs, including KMS-12-PE, OCI-MY5, and RPMI-8226R. In HMCLs, by real-time quantitative reverse transcription-polymerase chain reaction, methylation of EVL/miR-342 correlated with lower expression of both EVL (P = 0.013) and miR-342-3p (P = 0.023). Moreover, in KMS-12-PE and RPMI-8226R cells, both partially methylated for EVL/miR-342, 5-AzadC treatment led to demethylation of EVL/miR-342 and re-expression of miR-342-3p. Upon removal of 5-AzadC, continuous culture resulted in restoration of EVL/miR-342 methylation and downregulation of miR-342-3p. In primary samples, methylation of EVL/miR-342 was detected in 1 of 18 (5.6%) monoclonal gammopathy of undetermined significance (MGUS), 8 of 63 (12.7%) diagnostic MM, and 5 of 30 (16.7%) relapsed MM. EVL/miR-342 methylation was preferentially detected in IgD MM but not found to impact survival. Collectively, in MM, miR-342-3p is an intronic miRNA regulated by promoter DNA methylation of its host gene, EVL, in a tumor-specific manner. Methylation of EVL/miR-342 was present in consecutive stages of myelomagenesis including MGUS, diagnostic MM, and relapsed MM.-
dc.languageeng-
dc.publisherMosby, Inc. The Journal's web site is located at https://www.journals.elsevier.com/translational-research-
dc.relation.ispartofTranslational Research-
dc.titleEpigenetic silencing of EVL/miR-342 in multiple myeloma-
dc.typeArticle-
dc.identifier.emailWong, KY: kwanumu@hku.hk-
dc.identifier.emailChan, GCF: gcfchan@hku.hk-
dc.identifier.emailChim, CS: jcschim@hku.hk-
dc.identifier.authorityChan, GCF=rp00431-
dc.identifier.authorityChim, CS=rp00408-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.trsl.2017.11.005-
dc.identifier.pmid29242101-
dc.identifier.scopuseid_2-s2.0-85038375696-
dc.identifier.hkuros299555-
dc.identifier.volume192-
dc.identifier.spage46-
dc.identifier.epage53-
dc.identifier.isiWOS:000426026500004-
dc.publisher.placeUnited States-

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