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DDN-AS1-miR-15a/16-TCF3 反馈环调控宫颈癌的肿瘤进展。

DDN-AS1-miR-15a/16-TCF3 feedback loop regulates tumor progression in cervical cancer.

机构信息

Department of Gynecology, Wuhan Children's Hospital Affiliated by Tongji Medical College of Huazhong University of Science and Technology, Jiangan, Wuhan, Hubei, China.

Department of Gynecology, The Second People's Hospital of Nanhai District, Pingzhou, Guicheng, Nanhai, Foshan, Guangdong, China.

出版信息

J Cell Biochem. 2019 Jun;120(6):10228-10238. doi: 10.1002/jcb.28307. Epub 2018 Dec 23.

Abstract

Cervical cancer (CC) is known as one of the most common gynecological tumors. Long noncoding RNAs (lncRNAs) are a group of regulators that have been widely reported in human malignant tumors including CC. On the basis of the data of The Cancer Genome Atlas, lncRNA DDN and PRKAG1 antisense RNA 1 ( DDN-AS1) that is overexpressed in CC tissues predicted poor prognosis for patients with CC. Moreover, quantitative reverse transcription PCR analysis further identified the upregulation of DDN-AS1 in CC tissues and cell lines. Loss-of-function assays revealed that knockdown of DDN-AS1 suppressed CC progression by efficiently inhibiting cell proliferation, migration, and invasion. Mechanism investigations revealed that DDN-AS1 was upregulated by its upstream transcription activator transcription factor 3 ( TCF3). Moreover, DDN-AS1 increased the expression of  TCF3 by competitively binding miR-15a and miR-16. In conclusion, DDN-AS1-miR-15a/16-TCF3 feedback loop contributes to cell proliferation, migration, and invasion in CC.

摘要

宫颈癌(CC)是一种常见的妇科肿瘤。长链非编码 RNA(lncRNA)是一类在人类恶性肿瘤中广泛报道的调控因子,包括 CC。基于癌症基因组图谱的数据,lncRNA DDN 和 PRKAG1 反义 RNA 1(DDN-AS1)在 CC 组织中表达上调,预测 CC 患者预后不良。此外,定量逆转录 PCR 分析进一步鉴定出 DDN-AS1 在 CC 组织和细胞系中的上调。功能丧失实验表明,DDN-AS1 的敲低通过有效抑制细胞增殖、迁移和侵袭来抑制 CC 的进展。机制研究表明,DDN-AS1 由其上游转录激活因子转录因子 3(TCF3)上调。此外,DDN-AS1 通过竞争性结合 miR-15a 和 miR-16 增加 TCF3 的表达。总之,DDN-AS1-miR-15a/16-TCF3 反馈环促进了 CC 中的细胞增殖、迁移和侵袭。

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