Cai Lina, Wang Wuliang, Li Xiaomei, Dong Tieli, Zhang Qing, Zhu Baojv, Zhao Hu, Wu Shubiao
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
Department of Anesthesiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
Oncol Lett. 2018 Apr;15(4):5213-5219. doi: 10.3892/ol.2018.7937. Epub 2018 Feb 2.
Numerous studies have indicated that microRNAs (miRs), a group of small non-coding RNAs, are determining regulatory elements involved in the pathogenesis of various types of cancer, including cervical cancer (CC). Although miR-21-5p upregulation has been demonstrated to associate with tumorigenesis by controlling the expression of oncogenic and tumor suppressor genes, only a small number of studies have investigated the expression of miR-21-5p and its functional role in CC. The objective of the present study was to investigate the effect of miR-21-5p on the proliferation, apoptosis, migration and invasion of CC cells, and the potential underlying molecular mechanism of these effects. The measurement of miR-21-5p levels using quantitative polymerase chain reaction revealed that miR-21-5p was markedly increased in CC cell lines compared with normal cells. Upon silencing of miR-21-5p, a marked suppression of the proliferation, migration and invasion of CaSki cells was observed, with induction of cell apoptosis. These effects were reversed with miR-21-5p overexpression. A database search followed by a luciferase reporter assay ascertained that the 3'-untranslated region of the von Hippel-Lindau tumor suppressor (VHL) mRNA sequence was a direct target of miR-21-5p. Furthermore, silencing of VHL neutralized the effects of miR-21-5p inhibition. These observations suggested that miR-21-5p is an oncogene that is able to promote the metastatic phenotype of CC cells through downregulation of VHL expression, which may present a path to novel therapeutic stratagems for the CC therapy.
大量研究表明，微小RNA（miRs）作为一类小的非编码RNA，是参与包括宫颈癌（CC）在内的各种癌症发病机制的决定性调控元件。尽管已证明miR-21-5p的上调通过控制致癌基因和肿瘤抑制基因的表达与肿瘤发生相关，但仅有少数研究调查了miR-21-5p在CC中的表达及其功能作用。本研究的目的是探讨miR-21-5p对CC细胞增殖、凋亡、迁移和侵袭的影响，以及这些影响潜在的分子机制。使用定量聚合酶链反应测量miR-21-5p水平发现，与正常细胞相比，CC细胞系中miR-21-5p明显增加。沉默miR-21-5p后，观察到CaSki细胞的增殖、迁移和侵袭受到明显抑制，并诱导细胞凋亡。miR-21-5p过表达可逆转这些作用。通过数据库搜索及荧光素酶报告基因检测确定，冯·希佩尔-林道肿瘤抑制因子（VHL）mRNA序列的3'非翻译区是miR-21-5p的直接靶标。此外，沉默VHL可抵消miR-21-5p抑制的作用。这些观察结果表明，miR-21-5p是一种癌基因，能够通过下调VHL表达促进CC细胞的转移表型，这可能为CC治疗提供新的治疗策略途径。
