Sun Yu, Cheng Yan, Zhang Yan, Han Kun
Department of Obstetrics and Gynecology, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China.
Exp Ther Med. 2019 Aug;18(2):1440-1448. doi: 10.3892/etm.2019.7675. Epub 2019 Jun 14.
MicroRNAs (miRNAs) are frequently dysregulated in cervical cancer, and the aberrant regulation of miRNAs may be involved in the regulation of various cancer-associated biological processes. Therefore, further exploration of the specific roles of dysregulated miRNAs in cervical cancer and their associated mechanism may promote the development of effective therapeutic approaches. miRNA-889-3p (miR-889) serves crucial roles in esophageal squamous cell carcinoma and hepatocellular carcinoma. However, to the best of our knowledge, no studies concerning the relationship between miR-889 and cervical cancer were performed. The aims of this study were to measure miR-889 expression in cervical cancer and to examine the potential effects of miR-889 in cervical cancer development on a molecular level to provide potential clinical insight. The present study revealed that miR-889 was downregulated in cervical cancer tissues and cell lines. Reduced miR-889 expression was significantly associated with International Federation of Gynecology and Obstetrics cancer staging and with lymph node metastasis. In addition, miR-889 overexpression reduced cervical cancer cell viability and invasive ability. Using bioinformatics analysis, fibroblast growth factor receptor 2 (FGFR2) was predicted to be a potential target of miR-889, which was confirmed using luciferase reporter assay. Reverse transcription-quantitative PCR and western blot analysis results suggested that miR-889 overexpression decreased FGFR2 expression in cervical cancer cells at the mRNA and the protein level, respectively. Conversely, FGFR2 silencing using small interfering RNA imitated the tumor suppressive effects of miR-889 overexpression in cervical cancer cells, which was successfully reversed by plasmid-facilitated FGFR2 overexpression. These observations demonstrated that miR-889 may serve tumor suppressive roles in cervical cancer by directly targeting FGFR2, which indicated that this miRNA may be a promising therapeutic target for patients with cervical cancer.
微小RNA（miRNA）在宫颈癌中常常发生失调，而miRNA的异常调控可能参与多种癌症相关生物学过程的调节。因此，进一步探究失调的miRNA在宫颈癌中的具体作用及其相关机制，可能会推动有效治疗方法的发展。miRNA-889-3p（miR-889）在食管鳞状细胞癌和肝细胞癌中发挥着关键作用。然而，据我们所知，尚未有关于miR-889与宫颈癌关系的研究。本研究的目的是检测miR-889在宫颈癌中的表达，并在分子水平上研究miR-889对宫颈癌发展的潜在影响，以提供潜在的临床见解。本研究表明，miR-889在宫颈癌组织和细胞系中表达下调。miR-889表达降低与国际妇产科联盟（FIGO）癌症分期及淋巴结转移显著相关。此外，miR-889过表达降低了宫颈癌细胞的活力和侵袭能力。通过生物信息学分析预测成纤维细胞生长因子受体2（FGFR2）是miR-889的潜在靶标，荧光素酶报告基因检测证实了这一点。逆转录定量PCR和蛋白质印迹分析结果表明，miR-889过表达分别在mRNA和蛋白质水平上降低了宫颈癌细胞中FGFR2的表达。相反，使用小干扰RNA沉默FGFR2模拟了miR-889过表达对宫颈癌细胞的肿瘤抑制作用，而质粒介导的FGFR2过表达成功逆转了这种作用。这些观察结果表明，miR-889可能通过直接靶向FGFR2在宫颈癌中发挥肿瘤抑制作用，这表明该miRNA可能是宫颈癌患者有前景的治疗靶点。
