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Article: Epigenetic silencing of miR-342-3p in B cell lymphoma and its impact on autophagy

TitleEpigenetic silencing of miR-342-3p in B cell lymphoma and its impact on autophagy
Authors
KeywordsAutophagy
B cell lymphoma
DNA methylation
miR-342-3p
Tumor suppressor miRNA
Issue Date2020
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.clinicalepigeneticsjournal.com
Citation
Clinical Epigenetics, 2020, v. 12, p. article no. 150 How to Cite?
AbstractBackground: miR-342-3p, localized to 14q32, is a tumor suppressor miRNA implicated in carcinogenesis. Given the presence of a promotor-associated CpG island for its host gene, EVL, we hypothesized that intronic miR-342-3p is a tumor suppressor co-regulated with host gene by promoter DNA methylation in B cell lymphoma. Results: By bisulfite pyrosequencing-verified methylation-specific PCR (MSP), EVL/MIR342 methylation was detected in five (50%) lymphoma cell lines but not normal peripheral blood and tonsils. EVL/MIR342 methylation correlated with repression of both miR-342-3p and EVL in cell lines. In completely methylated SU-DHL-16 cells, 5-AzadC treatment resulted in promoter demethylation and re-expression of miR-342-3p and EVL. In 132 primary lymphoma samples, EVL/MIR342 was preferentially methylated in B cell lymphomas (N = 68; 68.7%) than T cell lymphoma (N = 8; 24.2%) by MSP (P < 0.0001). Moreover, EVL/MIR342 methylation was associated with lower miR-342-3p expression in 79 primary NHL (P = 0.0443). In SU-DHL-16 cells, the tumor suppressor function of miR-342-3p was demonstrated by the inhibition of cellular proliferation and increase of cell death upon over-expression of miR-342-3p. Mechanistically, overexpression of miR-342-3p resulted in a decrease of LC3-II, a biomarker of autophagy, which was pro-survival for SU-DHL-16. Pre-treatment with 3-methyladenine, an autophagy inhibitor, abrogated tumor suppression associated with miR-342-3p overexpression. By luciferase assay, MAP1LC3B, a precursor of LC3-II, was confirmed as a direct target of miR-342-3p. Finally, in SU-DHL-16 cells, overexpression of miR-342-3p downregulated the known target DNMT1, with promoter demethylation and re-expression of tumor suppressor E-cadherin. Conclusions: Intronic miR-342-3p is co-regulated with its host gene EVL by tumor-specific promoter DNA methylation in B cell lymphoma. The tumor suppressor function of miR-342-3p was mediated via inhibition of pro-survival autophagy by targeting MAP1LC3B and downregulation of DNMT1 with demethylation and re-expression of tumor suppressor genes.
Persistent Identifierhttp://hdl.handle.net/10722/295507
ISSN
2019 Impact Factor: 5.028
2015 SCImago Journal Rankings: 2.462
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, MY-
dc.contributor.authorCalin, GA-
dc.contributor.authorYuen, KS-
dc.contributor.authorJin, D-
dc.contributor.authorChim, CS-
dc.date.accessioned2021-01-25T11:15:52Z-
dc.date.available2021-01-25T11:15:52Z-
dc.date.issued2020-
dc.identifier.citationClinical Epigenetics, 2020, v. 12, p. article no. 150-
dc.identifier.issn1868-7075-
dc.identifier.urihttp://hdl.handle.net/10722/295507-
dc.description.abstractBackground: miR-342-3p, localized to 14q32, is a tumor suppressor miRNA implicated in carcinogenesis. Given the presence of a promotor-associated CpG island for its host gene, EVL, we hypothesized that intronic miR-342-3p is a tumor suppressor co-regulated with host gene by promoter DNA methylation in B cell lymphoma. Results: By bisulfite pyrosequencing-verified methylation-specific PCR (MSP), EVL/MIR342 methylation was detected in five (50%) lymphoma cell lines but not normal peripheral blood and tonsils. EVL/MIR342 methylation correlated with repression of both miR-342-3p and EVL in cell lines. In completely methylated SU-DHL-16 cells, 5-AzadC treatment resulted in promoter demethylation and re-expression of miR-342-3p and EVL. In 132 primary lymphoma samples, EVL/MIR342 was preferentially methylated in B cell lymphomas (N = 68; 68.7%) than T cell lymphoma (N = 8; 24.2%) by MSP (P < 0.0001). Moreover, EVL/MIR342 methylation was associated with lower miR-342-3p expression in 79 primary NHL (P = 0.0443). In SU-DHL-16 cells, the tumor suppressor function of miR-342-3p was demonstrated by the inhibition of cellular proliferation and increase of cell death upon over-expression of miR-342-3p. Mechanistically, overexpression of miR-342-3p resulted in a decrease of LC3-II, a biomarker of autophagy, which was pro-survival for SU-DHL-16. Pre-treatment with 3-methyladenine, an autophagy inhibitor, abrogated tumor suppression associated with miR-342-3p overexpression. By luciferase assay, MAP1LC3B, a precursor of LC3-II, was confirmed as a direct target of miR-342-3p. Finally, in SU-DHL-16 cells, overexpression of miR-342-3p downregulated the known target DNMT1, with promoter demethylation and re-expression of tumor suppressor E-cadherin. Conclusions: Intronic miR-342-3p is co-regulated with its host gene EVL by tumor-specific promoter DNA methylation in B cell lymphoma. The tumor suppressor function of miR-342-3p was mediated via inhibition of pro-survival autophagy by targeting MAP1LC3B and downregulation of DNMT1 with demethylation and re-expression of tumor suppressor genes.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.clinicalepigeneticsjournal.com-
dc.relation.ispartofClinical Epigenetics-
dc.rightsClinical Epigenetics. Copyright © BioMed Central Ltd.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAutophagy-
dc.subjectB cell lymphoma-
dc.subjectDNA methylation-
dc.subjectmiR-342-3p-
dc.subjectTumor suppressor miRNA-
dc.titleEpigenetic silencing of miR-342-3p in B cell lymphoma and its impact on autophagy-
dc.typeArticle-
dc.identifier.emailYuen, KS: samyuen@HKUCC-COM.hku.hk-
dc.identifier.emailJin, D: dyjin@hku.hk-
dc.identifier.authorityJin, D=rp00452-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s13148-020-00926-1-
dc.identifier.pmid33076962-
dc.identifier.pmcidPMC7574348-
dc.identifier.hkuros320945-
dc.identifier.volume12-
dc.identifier.spagearticle no. 150-
dc.identifier.epagearticle no. 150-
dc.identifier.isiWOS:000585100700001-
dc.publisher.placeUnited Kingdom-

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