MicroRNA-889-3p targets FGFR2 to inhibit cervical cancer cell viability and invasion

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.

Keywords: cervical cancer; fibroblast growth factor 2; invasion; microRNA-889-3p; viability.