Zhang Xia, Cai Dajun, Meng Lihua, Wang Bing
Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Oncol Rep. 2016 Oct;36(4):2321-8. doi: 10.3892/or.2016.5025. Epub 2016 Aug 17.
MicroRNA-124 (miR-124) was reported to be attenuated in human cervical cancer (CC) specimens. However, its role in CC remains elusive. In the present study, quantitative real-time PCR (qRT-PCR) analysis demonstrated that miR-124 expression is significantly downregulated in human CC tissues and several CC cell lines. Transfection of miR-124 mimics in CC cell lines HeLa and SiHa markedly inhibits cell proliferative, migratory and invasive capacities, as well as the epithelial-mesenchymal transition (EMT) process in vitro. Further studies have identified astrocyte-elevated gene-1 (AEG-1) as a direct target gene of miR-124. miR-124 downregulated AEG-1 expression through interaction with its 3'-untranslated regions (3'-UTRs), and miR-124 expression was inversely correlated with AEG-1 levels in CC specimens. Moreover, exogenous overexpression of AEG-1 significantly rescued the miR-124-induced inhibition of cell proliferation, migration and invasion, as well as the EMT process in HeLa cells. In conclusion, these findings suggested that miR-124 was able to suppress cell proliferation, invasion and migration, as well as the EMT process in cervical carcinomas through directly targeting AEG-1. miR-124 and AEG-1 may be potential therapeutic targets for the treatment of cervical carcinoma.
据报道,微小RNA-124(miR-124)在人宫颈癌(CC)标本中表达减弱。然而,其在宫颈癌中的作用仍不清楚。在本研究中,定量实时聚合酶链反应(qRT-PCR)分析表明,miR-124在人宫颈癌组织和几种宫颈癌细胞系中的表达显著下调。在宫颈癌细胞系HeLa和SiHa中转染miR-124模拟物可显著抑制细胞增殖、迁移和侵袭能力,以及体外上皮-间质转化(EMT)过程。进一步研究确定星形胶质细胞上调基因-1(AEG-1)是miR-124的直接靶基因。miR-124通过与其3'-非翻译区(3'-UTR)相互作用下调AEG-1表达,且在宫颈癌标本中miR-124表达与AEG-1水平呈负相关。此外,外源性过表达AEG-1可显著挽救miR-124诱导的HeLa细胞增殖、迁移和侵袭抑制以及EMT过程。总之,这些发现表明miR-124能够通过直接靶向AEG-1抑制宫颈癌细胞的增殖、侵袭和迁移以及EMT过程。miR-124和AEG-1可能是治疗宫颈癌的潜在治疗靶点。