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- Publisher Website: 10.1111/bjh.16517
- Scopus: eid_2-s2.0-85079864963
- PMID: 32079038
- WOS: WOS:000514541700001
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Article: Frequent methylation of the tumour suppressor miR‐1258 targeting PDL1: implication in multiple myeloma‐specific cytotoxicity and prognostification
Title | Frequent methylation of the tumour suppressor miR‐1258 targeting PDL1: implication in multiple myeloma‐specific cytotoxicity and prognostification |
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Authors | |
Keywords | DNA methylation miR-1258 myeloma PDL1 tumour suppressor |
Issue Date | 2020 |
Publisher | Wiley-Blackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJH |
Citation | British Journal of Haematology, 2020, v. 190 n. 2, p. 249-261 How to Cite? |
Abstract | miR-1258 is localised to the first intron of ZNF385B at chromosome 2q31.3. miR-1258 promoter methylation was studied in 147 samples including 10 normal buffy coat, eight normal bone marrow plasma cells, 16 human myeloma cell lines (HMCLs), 20 MGUS, 63 diagnostic myeloma, and 30 relapsed myeloma samples by methylation-specific PCR. In myeloma lines, miR-1258 methylation, verified by pyrosequencing, was detected in 62·5% HMCLs but not normal controls, and expression of miR-1258 correlated with that of ZNF385B. 5-Aza-2′-deoxycytidine resulted in promoter demethylation and ZNF385B/miR-1258 re-expression. Luciferase assay confirmed programmed cell death ligand-1 (PDL1) as a direct target of miR-1258. Over-expression of miR-1258 in completely methylated myeloma cells led to reduced cellular proliferation and enhanced apoptosis, hence a tumour suppressor role, in addition to repression of PDL1. In primary samples, miR-1258 methylation, with lower expression of miR-1258, was detected in 49·2% diagnostic myeloma, imparting an inferior PFS (P = 0·034) in addition to 50·0% relapsed myeloma but not MGUS. Therefore, miR-1258 is a tumour suppressor miRNA co-regulated with its host gene, and frequently hypermethylated in active myeloma instead of MGUS, hence acquired during myeloma progression. Methylation-mediated miR-1258 silencing led to overexpression of PDL1 and inferior PFS, implicating miR-1258 in the modulation of myeloma-specific cytotoxicity. |
Persistent Identifier | http://hdl.handle.net/10722/307680 |
ISSN | 2023 Impact Factor: 5.1 2023 SCImago Journal Rankings: 1.574 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Wang, LQ | - |
dc.contributor.author | Kumar, S | - |
dc.contributor.author | Calin, GA | - |
dc.contributor.author | LI, Z | - |
dc.contributor.author | Chim, CS | - |
dc.date.accessioned | 2021-11-12T13:36:14Z | - |
dc.date.available | 2021-11-12T13:36:14Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | British Journal of Haematology, 2020, v. 190 n. 2, p. 249-261 | - |
dc.identifier.issn | 0007-1048 | - |
dc.identifier.uri | http://hdl.handle.net/10722/307680 | - |
dc.description.abstract | miR-1258 is localised to the first intron of ZNF385B at chromosome 2q31.3. miR-1258 promoter methylation was studied in 147 samples including 10 normal buffy coat, eight normal bone marrow plasma cells, 16 human myeloma cell lines (HMCLs), 20 MGUS, 63 diagnostic myeloma, and 30 relapsed myeloma samples by methylation-specific PCR. In myeloma lines, miR-1258 methylation, verified by pyrosequencing, was detected in 62·5% HMCLs but not normal controls, and expression of miR-1258 correlated with that of ZNF385B. 5-Aza-2′-deoxycytidine resulted in promoter demethylation and ZNF385B/miR-1258 re-expression. Luciferase assay confirmed programmed cell death ligand-1 (PDL1) as a direct target of miR-1258. Over-expression of miR-1258 in completely methylated myeloma cells led to reduced cellular proliferation and enhanced apoptosis, hence a tumour suppressor role, in addition to repression of PDL1. In primary samples, miR-1258 methylation, with lower expression of miR-1258, was detected in 49·2% diagnostic myeloma, imparting an inferior PFS (P = 0·034) in addition to 50·0% relapsed myeloma but not MGUS. Therefore, miR-1258 is a tumour suppressor miRNA co-regulated with its host gene, and frequently hypermethylated in active myeloma instead of MGUS, hence acquired during myeloma progression. Methylation-mediated miR-1258 silencing led to overexpression of PDL1 and inferior PFS, implicating miR-1258 in the modulation of myeloma-specific cytotoxicity. | - |
dc.language | eng | - |
dc.publisher | Wiley-Blackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJH | - |
dc.relation.ispartof | British Journal of Haematology | - |
dc.rights | Submitted (preprint) Version 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 Use of Self-Archived Versions. Accepted (peer-reviewed) Version 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 Use of Self-Archived Versions. | - |
dc.subject | DNA methylation | - |
dc.subject | miR-1258 | - |
dc.subject | myeloma | - |
dc.subject | PDL1 | - |
dc.subject | tumour suppressor | - |
dc.title | Frequent methylation of the tumour suppressor miR‐1258 targeting PDL1: implication in multiple myeloma‐specific cytotoxicity and prognostification | - |
dc.type | Article | - |
dc.identifier.email | Wang, LQ: wanglucy@hku.hk | - |
dc.identifier.email | Chim, CS: jcschim@HKUCC-COM.hku.hk | - |
dc.identifier.authority | Chim, CS=rp00408 | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1111/bjh.16517 | - |
dc.identifier.pmid | 32079038 | - |
dc.identifier.scopus | eid_2-s2.0-85079864963 | - |
dc.identifier.hkuros | 329788 | - |
dc.identifier.volume | 190 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 249 | - |
dc.identifier.epage | 261 | - |
dc.identifier.isi | WOS:000514541700001 | - |
dc.publisher.place | United Kingdom | - |