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异常甲基化介导的lncRNA下调促进宫颈癌细胞增殖。

Aberrant methylation-mediated downregulation of lncRNA promotes cell proliferation in cervical cancer.

作者信息

Zhao Chengcheng, Liu Jian, Wu Huazhang, Hu Jiaojiao, Chen Jianquan, Chen Jie, Qiao Fengchang

机构信息

Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

Central Laboratory, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China.

出版信息

J Biol Res (Thessalon). 2020 Jun 26;27:11. doi: 10.1186/s40709-020-00122-5. eCollection 2020 Dec.

Abstract

BACKGROUND

Long non-coding RNA (lncRNA) plays an important role in tumorigenesis. The lncRNA 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 in cervical cancer. Expression of 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 was investigated by overexpressing or silencing 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 promoter methylation status in cervical cancer cells.

RESULTS

expression was lower in cervical cancer compared with normal cervical tissues, and the level was significantly correlated with the patient age and tumor size. overexpression inhibited the proliferation and cell cycle progression of HeLa cells in vitro and/or in vivo, whereas silencing had the opposite effects. 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 promoter.

CONCLUSION

expression is downregulated in cervical cancer, potentially through increased promoter methylation, and the upregulation of expression inhibited tumor growth. These data suggest that could be a diagnostic marker and potential therapeutic target for cervical cancer.

摘要

背景

长链非编码RNA(lncRNA)在肿瘤发生过程中发挥重要作用。已有研究表明lncRNA参与多种肿瘤的生长;然而,其在宫颈癌中的作用尚未阐明。本研究旨在探讨lncRNA在宫颈癌中的表达、功能及潜在作用机制。通过定量实时聚合酶链反应(qRT-PCR)检测lncRNA在宫颈癌组织及癌旁正常宫颈组织中的表达,并对来自基因表达谱交互分析(GEPIA)数据库的数据进行生物信息学分析。通过在HeLa和SiHa宫颈癌细胞中过表达或沉默lncRNA,随后进行体外和体内分析,研究lncRNA的功能。采用甲基化特异性PCR(MSP)和亚硫酸氢盐基因组测序(BGS)检测宫颈癌细胞中lncRNA启动子的甲基化状态。

结果

与正常宫颈组织相比,lncRNA在宫颈癌中的表达较低,且其表达水平与患者年龄和肿瘤大小显著相关。lncRNA过表达在体外和/或体内抑制HeLa细胞的增殖和细胞周期进程,而lncRNA沉默则产生相反效果。用DNA甲基转移酶抑制剂5'-氮杂胞苷(5'-Aza)处理宫颈癌细胞后,lncRNA表达升高,这至少部分是通过lncRNA启动子处CpG甲基化减少介导的。

结论

lncRNA在宫颈癌中的表达下调,可能是由于lncRNA启动子甲基化增加,lncRNA表达上调抑制肿瘤生长。这些数据表明lncRNA可能是宫颈癌的诊断标志物和潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c4d/7318366/bdb9c7cf8b9b/40709_2020_122_Fig1_HTML.jpg

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