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Article: Epigenetic silencing of LPP/miR-28 in multiple myeloma
Title | Epigenetic silencing of LPP/miR-28 in multiple myeloma |
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Authors | |
Keywords | Haematology Molecular Genetics Myeloma Tumour Biology |
Issue Date | 2018 |
Publisher | BMJ Publishing Group. The Journal's web site is located at http://jcp.bmjjournals.com/ |
Citation | Journal of Clinical Pathology, 2018, v. 71 n. 3, p. 253-258 How to Cite? |
Abstract | Aims miR-28-5- is a tumour suppressor microRNA implicated in cancers. As a CpG island is absent in miR-28-5- but present in its host gene, LPP (LIM domain containing preferred translocation partner in lipoma), we hypothesized that miR-28-5p is epigenetically silenced by promoter DNA methylation of its host gene in multiple myeloma.
Methods Methylation-specific PCR, verified by quantitative bisulfite pyrosequencing, was employed to study methylation of LPP/miR-28 in healthy controls (n=10), human myeloma cell lines (HMCLs) (n=15), and primary myeloma marrow samples at diagnosis (n=49) and at relapse (n=18). Quantitative reverse transcription PCR was used to investigate expression of miR-28-5p, LPP and CCND1.
Results LPP/miR-28 was completely unmethylated in all healthy controls and 12 (80%) HMCLs, but partially methylated in three (20%) HMCLs. Methylation of LPP/miR-28 correlated with low expression of miR-285p (p=0.012) and LPP (p=0.037) in HMCLs. In RPMI-8226R cells, in which LPP/miR-28 was partially methylated, 5-AzadC treatment led to demethylation of LPP/miR-28 and re-expression of both miR-28-5p (p=0.0007) and LPP (p=0.0007), whereas continuous culture without 5-AzadC restored LPP/miR-28 methylation and reduced expression of both miR-28-5p (p=0.0013) and LPP (p=0.0025). Moreover, a known miR-28-5p target, CCND1, was expressed at higher levels in HMCLs with LPP/miR-28 methylation than those without, consistent with a tumour suppressor role of miR-28-5p in myeloma. However, in primary samples, LPP/miR-28 was methylated in two (4.1%) at diagnosis, whereas none at relapse.
Conclusions This is the first report of epigenetic regulation of the intronic miR-28-5p expression by promoter DNA methylation of its host gene, hence warrants further study in different cancers. |
Persistent Identifier | http://hdl.handle.net/10722/271997 |
ISSN | 2023 Impact Factor: 2.5 2023 SCImago Journal Rankings: 0.934 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | LI, Z | - |
dc.contributor.author | Wong, KY | - |
dc.contributor.author | Chan, GCF | - |
dc.contributor.author | Chim, JCS | - |
dc.date.accessioned | 2019-07-20T10:33:40Z | - |
dc.date.available | 2019-07-20T10:33:40Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Journal of Clinical Pathology, 2018, v. 71 n. 3, p. 253-258 | - |
dc.identifier.issn | 0021-9746 | - |
dc.identifier.uri | http://hdl.handle.net/10722/271997 | - |
dc.description.abstract | Aims miR-28-5- is a tumour suppressor microRNA implicated in cancers. As a CpG island is absent in miR-28-5- but present in its host gene, LPP (LIM domain containing preferred translocation partner in lipoma), we hypothesized that miR-28-5p is epigenetically silenced by promoter DNA methylation of its host gene in multiple myeloma. Methods Methylation-specific PCR, verified by quantitative bisulfite pyrosequencing, was employed to study methylation of LPP/miR-28 in healthy controls (n=10), human myeloma cell lines (HMCLs) (n=15), and primary myeloma marrow samples at diagnosis (n=49) and at relapse (n=18). Quantitative reverse transcription PCR was used to investigate expression of miR-28-5p, LPP and CCND1. Results LPP/miR-28 was completely unmethylated in all healthy controls and 12 (80%) HMCLs, but partially methylated in three (20%) HMCLs. Methylation of LPP/miR-28 correlated with low expression of miR-285p (p=0.012) and LPP (p=0.037) in HMCLs. In RPMI-8226R cells, in which LPP/miR-28 was partially methylated, 5-AzadC treatment led to demethylation of LPP/miR-28 and re-expression of both miR-28-5p (p=0.0007) and LPP (p=0.0007), whereas continuous culture without 5-AzadC restored LPP/miR-28 methylation and reduced expression of both miR-28-5p (p=0.0013) and LPP (p=0.0025). Moreover, a known miR-28-5p target, CCND1, was expressed at higher levels in HMCLs with LPP/miR-28 methylation than those without, consistent with a tumour suppressor role of miR-28-5p in myeloma. However, in primary samples, LPP/miR-28 was methylated in two (4.1%) at diagnosis, whereas none at relapse. Conclusions This is the first report of epigenetic regulation of the intronic miR-28-5p expression by promoter DNA methylation of its host gene, hence warrants further study in different cancers. | - |
dc.language | eng | - |
dc.publisher | BMJ Publishing Group. The Journal's web site is located at http://jcp.bmjjournals.com/ | - |
dc.relation.ispartof | Journal of Clinical Pathology | - |
dc.rights | Journal of Clinical Pathology. Copyright © BMJ Publishing Group. | - |
dc.rights | This article has been accepted for publication in [Journal, Year] following peer review, and the Version of Record can be accessed online at [insert full DOI eg. http://dx.doi.org/10.1136/xxxxx]. [© Authors (or their employer(s)) OR © BMJ Publishing Group Ltd ( for assignments of BMJ Case Reports)] <year> | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Haematology | - |
dc.subject | Molecular Genetics | - |
dc.subject | Myeloma | - |
dc.subject | Tumour Biology | - |
dc.title | Epigenetic silencing of LPP/miR-28 in multiple myeloma | - |
dc.type | Article | - |
dc.identifier.email | Wong, KY: kwanumu@hku.hk | - |
dc.identifier.email | Chan, GCF: gcfchan@hku.hk | - |
dc.identifier.email | Chim, JCS: jcschim@hku.hk | - |
dc.identifier.authority | Chan, GCF=rp00431 | - |
dc.identifier.authority | Chim, JCS=rp00408 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1136/jclinpath-2017-204501 | - |
dc.identifier.pmid | 28775176 | - |
dc.identifier.scopus | eid_2-s2.0-85041523024 | - |
dc.identifier.hkuros | 299560 | - |
dc.identifier.volume | 71 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | 253 | - |
dc.identifier.epage | 258 | - |
dc.identifier.isi | WOS:000429094200010 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 0021-9746 | - |