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Metformin regulates expression of DNA methyltransferases through the miR-148/-152 family in non-small lung cancer cells
DC Field | Value | Language |
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dc.contributor.author | 김동호 | - |
dc.date.accessioned | 2024-05-30T07:12:27Z | - |
dc.date.available | 2024-05-30T07:12:27Z | - |
dc.date.issued | 2023-03 | - |
dc.identifier.issn | 1868-7075 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/199640 | - |
dc.description.abstract | BackgroundTo understand the molecular mechanisms involved in regulation of DNA methyltransferases (DNMTs) by metformin in non-small cell lung cancer (NSCLC) cells.MethodsExpression levels of DNMTs in response to metformin were analyzed in NSCLC cells. MicroRNAs regulating expression of DNMTs at the post-transcriptional level were searched using miRNA-target databases (miRDB and miRTarBase), TCGA RNASeqV2 lung cancer data, and miRNA-seq.ResultsMetformin dose-dependently downregulated expression of DNMT1 and DNMT3a at the post-transcriptional level and expression of DNMT3b at the transcriptional level in A549 lung cancer cells. Activity of DNMTs was reduced by about 2.6-fold in A549 cells treated with 10 mM metformin for 72 h. miR-148/-152 family members (miR-148a, miR-148b, and miR-152) targeting the 3 ' UTR of DNMTs were associated with post-transcriptional regulation of DNMTs by metformin. Metformin upregulated expression of miR-148a, miR-148b, and miR-152 in A549 and H1650 cells. Transfection with an miR-148b plasmid or a mimic suppressed expression of DNMT1 and DNMT3b in A549 cells. Transfection with the miR-148a mimic in A549 and H1650 cells decreased the luciferase activity of DNMT1 3 ' UTR. A combination of metformin and cisplatin synergistically increased expression levels of miR-148/-152 family members but decreased expression of DNMTs in A549 cells. Low expression of miR-148b was associated with poor overall survival (HR = 2.56, 95% CI 1.09-6.47; P = 0.04) but not with recurrence-free survival.ConclusionsThe present study suggests that metformin inhibits expression of DNMTs by upregulating miR-148/-152 family members in NSCLC cells. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | BiomedCentral | - |
dc.relation.isPartOf | CLINICAL EPIGENETICS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | 3' Untranslated Regions | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung* / drug therapy | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung* / genetics | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung* / metabolism | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Cell Proliferation | - |
dc.subject.MESH | DNA / metabolism | - |
dc.subject.MESH | DNA Methylation | - |
dc.subject.MESH | DNA Modification Methylases / genetics | - |
dc.subject.MESH | Gene Expression Regulation, Neoplastic | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Lung Neoplasms* / drug therapy | - |
dc.subject.MESH | Lung Neoplasms* / genetics | - |
dc.subject.MESH | Lung Neoplasms* / metabolism | - |
dc.subject.MESH | Metformin* / pharmacology | - |
dc.subject.MESH | MicroRNAs* / genetics | - |
dc.subject.MESH | MicroRNAs* / metabolism | - |
dc.title | Metformin regulates expression of DNA methyltransferases through the miR-148/-152 family in non-small lung cancer cells | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Others | - |
dc.contributor.googleauthor | Bo Bin Lee | - |
dc.contributor.googleauthor | Dongho Kim | - |
dc.contributor.googleauthor | Yujin Kim | - |
dc.contributor.googleauthor | Joungho Han | - |
dc.contributor.googleauthor | Young Mog Shim | - |
dc.contributor.googleauthor | Duk-Hwan Kim | - |
dc.identifier.doi | 10.1186/s13148-023-01466-0 | - |
dc.contributor.localId | A06577 | - |
dc.relation.journalcode | J03332 | - |
dc.identifier.eissn | 1868-7083 | - |
dc.identifier.pmid | 36959680 | - |
dc.subject.keyword | DNMTs | - |
dc.subject.keyword | Lung cancer | - |
dc.subject.keyword | Metformin | - |
dc.subject.keyword | Survival | - |
dc.subject.keyword | microRNAs | - |
dc.contributor.alternativeName | Kim, Dongho | - |
dc.contributor.affiliatedAuthor | 김동호 | - |
dc.citation.volume | 15 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 48 | - |
dc.identifier.bibliographicCitation | CLINICAL EPIGENETICS, Vol.15(1) : 48, 2023-03 | - |
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