{"title":"Aberrant methylation-mediated downregulation of lncRNA <i>CCND2 AS1</i> promotes cell proliferation in cervical cancer.","authors":"Chengcheng Zhao, Jian Liu, Huazhang Wu, Jiaojiao Hu, Jianquan Chen, Jie Chen, Fengchang Qiao","doi":"10.1186/s40709-020-00122-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNA (lncRNA) plays an important role in tumorigenesis. The lncRNA <i>CCND2 AS1</i> has been shown to be involved in the growth of several tumors; however, its role in cervical cancer has not been elucidated. This study aimed to explore the expression, function, and underlying mechanism of action of <i>CCND2 AS1</i> in cervical cancer. Expression of <i>CCND2 AS1</i> was examined in cervical cancer and adjacent normal cervical tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and by bioinformatic analysis of data from the Gene Expression Profiling Interactive Analysis (GEPIA) database. The function of <i>CCND2 AS1</i> was investigated by overexpressing or silencing <i>CCND2 AS1</i> in HeLa and SiHa cervical cancer cells followed by in vitro and in vivo analyses. Methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS) were used to detect <i>CCND2 AS1</i> promoter methylation status in cervical cancer cells.</p><p><strong>Results: </strong><i>CCND2 AS1</i> expression was lower in cervical cancer compared with normal cervical tissues, and the level was significantly correlated with the patient age and tumor size. <i>CCND2 AS1</i> overexpression inhibited the proliferation and cell cycle progression of HeLa cells in vitro and/or in vivo, whereas <i>CCND2 AS1</i> silencing had the opposite effects. <i>CCND2 AS1</i> expression was elevated after treatment of cervical cancer cells with the DNA methyltransferase inhibitor 5'-azacytidine (5'-Aza), and this was mediated, at least in part, via reduced CpG methylation at the <i>CCND2 AS1</i> promoter.</p><p><strong>Conclusion: </strong><i>CCND2 AS1</i> expression is downregulated in cervical cancer, potentially through increased <i>CCND2 AS1</i> promoter methylation, and the upregulation of <i>CCND2 AS1</i> expression inhibited tumor growth. These data suggest that <i>CCND2 AS1</i> could be a diagnostic marker and potential therapeutic target for cervical cancer.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2020-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40709-020-00122-5","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s40709-020-00122-5","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/12/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 2
Abstract
Background: Long non-coding RNA (lncRNA) plays an important role in tumorigenesis. The lncRNA CCND2 AS1 has been shown to be involved in the growth of several tumors; however, its role in cervical cancer has not been elucidated. This study aimed to explore the expression, function, and underlying mechanism of action of CCND2 AS1 in cervical cancer. Expression of CCND2 AS1 was examined in cervical cancer and adjacent normal cervical tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and by bioinformatic analysis of data from the Gene Expression Profiling Interactive Analysis (GEPIA) database. The function of CCND2 AS1 was investigated by overexpressing or silencing CCND2 AS1 in HeLa and SiHa cervical cancer cells followed by in vitro and in vivo analyses. Methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS) were used to detect CCND2 AS1 promoter methylation status in cervical cancer cells.
Results: CCND2 AS1 expression was lower in cervical cancer compared with normal cervical tissues, and the level was significantly correlated with the patient age and tumor size. CCND2 AS1 overexpression inhibited the proliferation and cell cycle progression of HeLa cells in vitro and/or in vivo, whereas CCND2 AS1 silencing had the opposite effects. CCND2 AS1 expression was elevated after treatment of cervical cancer cells with the DNA methyltransferase inhibitor 5'-azacytidine (5'-Aza), and this was mediated, at least in part, via reduced CpG methylation at the CCND2 AS1 promoter.
Conclusion: CCND2 AS1 expression is downregulated in cervical cancer, potentially through increased CCND2 AS1 promoter methylation, and the upregulation of CCND2 AS1 expression inhibited tumor growth. These data suggest that CCND2 AS1 could be a diagnostic marker and potential therapeutic target for cervical cancer.
期刊介绍：
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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