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HOTAIR Induces Methylation of PCDH10, a Tumor Suppressor Gene, by Regulating DNMT1 and Sponging with miR-148b in Gastric Adenocarcinoma
DC Field | Value | Language |
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dc.contributor.author | 이상길 | - |
dc.date.accessioned | 2021-12-28T17:06:04Z | - |
dc.date.available | 2021-12-28T17:06:04Z | - |
dc.date.issued | 2021-02 | - |
dc.identifier.issn | 0513-5796 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/186935 | - |
dc.description.abstract | Purpose: HOX transcript antisense intergenic RNA (HOTAIR), as a long non-coding RNA, has been reported to regulate carcinogenesis by epigenetic mechanism in various cancers. Protocadherin 10 (PCDH10) is one of the well-known tumor suppressor genes, and is frequently methylated in gastric cancers (GC). We aimed to investigate the detailed pathway of how HOTAIR contributes to the target gene in gastric carcinogenesis. Materials and methods: We investigated the mechanism of HOTAIR on carcinogenesis and metastasis of GC. Methylation-specific PCR was performed to identify the interaction between HOTAIR and PCDH10. In addition, we investigated the interaction between miR-148b and HOTAIR by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results: The expression of HOTAIR was significantly upregulated in GC tissues (p<0.05) and GC cell lines (p<0.01), while PCDH10 was downregulated in GC tissues (p<0.05). The knockdown of HOTAIR (si-HOTAIR1 and 2) significantly upregulated the mRNA/protein expression of PCDH10 and reduced the methylation of PCDH10 compared to the control in MKN 28 and MKN 74. Si-HOTAIR1 and 2 significantly reduced DNA methyltransferase 1 (DNMT1) expression, and overexpression of HOTAIR increased DNMT1 expression. In RIP, we found that miR-148b interacted with HOTAIR. Si-HOTAIRs increased miR-148b expression, and miR-148b mimic inversely reduced HOTAIR expression. Si-HOTAIRs and miR-148b mimic reduced DNMT1 expression and increased PCDH10 expression compared to the control. Conclusion: This study demonstrated that HOTAIR interacts with miR-148b and DNMT1, eventually leading to PCDH10 methylation, which contributes to the progression of GC. Our findings provide a better understanding for detailed pathway of HOTAIR in epigenetic mechanism of GC. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Yonsei University | - |
dc.relation.isPartOf | YONSEI MEDICAL JOURNAL | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Adenocarcinoma / genetics* | - |
dc.subject.MESH | Apoptosis / genetics | - |
dc.subject.MESH | Cadherins / genetics* | - |
dc.subject.MESH | Cadherins / metabolism | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Cell Movement / genetics | - |
dc.subject.MESH | Cell Proliferation / genetics | - |
dc.subject.MESH | DNA (Cytosine-5-)-Methyltransferase 1 / metabolism* | - |
dc.subject.MESH | DNA Methylation / genetics* | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Gene Expression Regulation, Neoplastic | - |
dc.subject.MESH | Genes, Tumor Suppressor* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | MicroRNAs / genetics | - |
dc.subject.MESH | MicroRNAs / metabolism* | - |
dc.subject.MESH | Middle Aged | - |
dc.subject.MESH | Neoplasm Invasiveness | - |
dc.subject.MESH | Protocadherins | - |
dc.subject.MESH | RNA, Long Noncoding / genetics* | - |
dc.subject.MESH | Stomach Neoplasms / genetics* | - |
dc.subject.MESH | Stomach Neoplasms / pathology | - |
dc.title | HOTAIR Induces Methylation of PCDH10, a Tumor Suppressor Gene, by Regulating DNMT1 and Sponging with miR-148b in Gastric Adenocarcinoma | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Seung In Seo | - |
dc.contributor.googleauthor | Jung Ho Yoon | - |
dc.contributor.googleauthor | Hyo Joo Byun | - |
dc.contributor.googleauthor | Sang Kil Lee | - |
dc.identifier.doi | 10.3349/ymj.2021.62.2.118 | - |
dc.contributor.localId | A02812 | - |
dc.relation.journalcode | J02813 | - |
dc.identifier.eissn | 1976-2437 | - |
dc.identifier.pmid | 33527791 | - |
dc.subject.keyword | HOX transcript antisense intergenic RNA (HOTAIR) | - |
dc.subject.keyword | gastric cancer | - |
dc.subject.keyword | methylation | - |
dc.subject.keyword | microRNA 148b | - |
dc.subject.keyword | protocadherin 10 | - |
dc.contributor.alternativeName | Lee, Sang Kil | - |
dc.contributor.affiliatedAuthor | 이상길 | - |
dc.citation.volume | 62 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 118 | - |
dc.citation.endPage | 128 | - |
dc.identifier.bibliographicCitation | YONSEI MEDICAL JOURNAL, Vol.62(2) : 118-128, 2021-02 | - |
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