Tao Pingping, Wen Hao, Yang Binlie, Zhang Ai, Wu Xiaohua, Li Qing
Department of Obstetrics and Gynecology, People's Hospital of Shanghai Pudong New Area, Shanghai 201299, P.R. China.
Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
Exp Ther Med. 2018 Jan;15(1):562-568. doi: 10.3892/etm.2017.5392. Epub 2017 Oct 30.
MicroRNAs (miRs) are aberrantly expressed in various cancer types and have critical roles in their genesis and progression. miR-144 has been identified to be involved in the development of hepatocellular carcinoma and rectal cancer. However, the roles of miR-144 in cervical cancer and the underlying molecular mechanisms have remained elusive. The present study identified that miR-144 was significantly decreased in cervical cancer tissues compared with that in matched normal cervical tissues as well as in metastatic vs. non-metastatic cervical cancer tissues. miR-144 downregulation was significantly associated with the International Federation of Gynecology and Obstetrics stage and lymph node metastasis. In a gain-of function study, miR-144 mimics were transfected into the Hela and C33A cervical cancer cell lines, which led to suppression of cell growth. In addition, overexpression of miR-144 inhibited the migration and invasion of Hela and C33A cells. Furthermore, a bioinformatics analysis identified vascular endothelial growth factor A (VEGFA) VEGFC as two novel target genes of miR-144. Of note, a dual luciferase reporter assay, reverse-transcription quantitative polymerase chain reaction analysis and western blot analysis demonstrated that miR-144 repressed the expression of VEGFA and VEGFC by directly targeting to their 3'-untranslated region. Taken together, the results suggested that miR-144 acts as a tumor suppressor in the proliferation and metastasis of cervical cancer cells by directly targeting VEGFA and VEGFC, suggesting that miR-144 may be a novel promising diagnostic and therapeutic biomarker for cervical cancer.
微小RNA(miR)在多种癌症类型中表达异常,并在其发生和发展中起关键作用。已确定miR-144参与肝细胞癌和直肠癌的发展。然而,miR-144在宫颈癌中的作用及其潜在分子机制仍不清楚。本研究发现,与配对的正常宫颈组织以及转移性与非转移性宫颈癌组织相比,miR-144在宫颈癌组织中显著降低。miR-144下调与国际妇产科联盟分期和淋巴结转移显著相关。在功能获得性研究中,将miR-144模拟物转染到Hela和C33A宫颈癌细胞系中,导致细胞生长受到抑制。此外,miR-144的过表达抑制了Hela和C33A细胞的迁移和侵袭。此外,生物信息学分析确定血管内皮生长因子A(VEGFA)和VEGFC是miR-144的两个新靶基因。值得注意的是,双荧光素酶报告基因检测、逆转录定量聚合酶链反应分析和蛋白质印迹分析表明,miR-144通过直接靶向VEGFA和VEGFC的3'-非翻译区来抑制它们的表达。综上所述,结果表明miR-144通过直接靶向VEGFA和VEGFC在宫颈癌细胞的增殖和转移中发挥肿瘤抑制作用,提示miR-144可能是一种新的有前景的宫颈癌诊断和治疗生物标志物。