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. 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. 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.

中文翻译：

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异常甲基化介导的 lncRNA CCND2 AS1 下调促进宫颈癌细胞增殖。

长链非编码 RNA (lncRNA) 在肿瘤发生中起重要作用。lncRNA CCND2 AS1 已被证明与几种肿瘤的生长有关。然而，它在宫颈癌中的作用尚未阐明。本研究旨在探讨CCND2 AS1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) 和来自基因表达谱交互分析 (GEPIA) 数据库的数据的生物信息学分析，检查了 CCND2 AS1 在宫颈癌和邻近的正常宫颈组织中的表达。通过在 HeLa 和 SiHa 宫颈癌细胞中过表达或沉默 CCND2 AS1，然后进行体外和体内分析，研究了 CCND2 AS1 的功能。甲基化特异性 PCR (MSP) 和亚硫酸氢盐基因组测序 (BGS) 用于检测宫颈癌细胞中 CCND2 AS1 启动子甲基化状态。CCND2 AS1在宫颈癌组织中的表达低于正常宫颈组织，其水平与患者年龄和肿瘤大小显着相关。CCND2 AS1 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 CCND2 AS1 沉默具有相反的作用。在用 DNA 甲基转移酶抑制剂 5'-氮杂胞苷 (5'-Aza) 处理宫颈癌细胞后，CCND2 AS1 表达升高，这至少部分是通过减少 CCND2 AS1 启动子处的 CpG 甲基化来介导的。CCND2 AS1 表达在宫颈癌中下调，可能是通过增加 CCND2 AS1 启动子甲基化，CCND2 AS1 表达的上调抑制了肿瘤的生长。这些数据表明CCND2 AS1可能是宫颈癌的诊断标志物和潜在的治疗靶点。