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长链非编码 RNA SOX21-AS1 通过竞争性吸附 miR-7/VDAC1 促进宫颈癌进展。

Long noncoding RNA SOX21-AS1 promotes cervical cancer progression by competitively sponging miR-7/VDAC1.

机构信息

Department of Obstetrics and Gynecology, the first Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

出版信息

J Cell Physiol. 2019 Aug;234(10):17494-17504. doi: 10.1002/jcp.28371. Epub 2019 Mar 25.

DOI:10.1002/jcp.28371
PMID:30912129
Abstract

Growing evidence has shown that long noncoding RNAs (lncRNAs) play crucial roles in cervical cancer. Dy000sregulation of lncRNA SOX21 antisense RNA 1 (SOX21-AS1) has been reported in several tumors. However, its expression pattern and potential biological function in cervical cancer (CC) have not been investigated. In this study, we first reported that SOX21-AS1 expression was significantly upregulated in both CC tissues and cell lines. High expression of SOX21-AS1 was found to be significantly correlated with Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis and depth of cervical invasion. Further clinical assay confirmed that high SOX21-AS1 expression was associated with shorter overall survival and could be used as a potential prognostic biomarker for CC patients. Functional investigation showed that knockdown of SOX21-AS1 suppressed CC cells proliferation, migration, and invasion, as well as epithelial to mesenchymal transition progress. Furthermore, our data showed that microRNA-7 (miR-7) interacted with SOX21-AS1 by directly targeting the miRNA-binding site in the SOX21-AS1 sequence, and quantitative real-time polymerase chain reaction results showed overexpression of SOX21-AS1 decreased the levels of miR-7 in CC cells. Moreover, we confirmed that miR-7 directly targeted the 3'-untranslated region of voltage dependent anion channel 1 (VDAC1). Final in vitro assay suggested that in CC cells with SOX21-AS1, VDAC1 overexpression resulted in an increase of cell proliferation, migration, and invasion. Overall, our findings illuminate how SOX21-AS1 formed a regulatory network to confer an oncogenic function in CC and SOX21-AS1 could be regarded as an efficient therapeutic target and potential biomarker for CC patients.

摘要

越来越多的证据表明,长非编码 RNA(lncRNA)在宫颈癌中发挥着关键作用。在几种肿瘤中已经报道了 lncRNA SOX21 反义 RNA 1(SOX21-AS1)的 Dy000s 调节。然而,其在宫颈癌(CC)中的表达模式和潜在生物学功能尚未被研究。在这项研究中,我们首次报道 SOX21-AS1 在 CC 组织和细胞系中的表达显著上调。发现 SOX21-AS1 的高表达与妇产科联合会(FIGO)分期、淋巴结转移和宫颈浸润深度显著相关。进一步的临床检测证实,SOX21-AS1 高表达与总生存期缩短有关,可作为 CC 患者的潜在预后生物标志物。功能研究表明,SOX21-AS1 的敲低抑制了 CC 细胞的增殖、迁移和侵袭,以及上皮间质转化过程。此外,我们的数据表明 microRNA-7(miR-7)通过直接靶向 SOX21-AS1 序列中的 miRNA 结合位点与 SOX21-AS1 相互作用,实时定量聚合酶链反应结果显示 SOX21-AS1 的过表达降低了 CC 细胞中 miR-7 的水平。此外,我们证实 miR-7 直接靶向电压依赖性阴离子通道 1(VDAC1)的 3'非翻译区。最终的体外实验表明,在具有 SOX21-AS1 的 CC 细胞中,VDAC1 的过表达导致细胞增殖、迁移和侵袭增加。总的来说,我们的研究结果阐明了 SOX21-AS1 如何形成一个调节网络,赋予 CC 致癌功能,SOX21-AS1 可被视为 CC 患者的有效治疗靶点和潜在生物标志物。

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