MicroRNA-432 is downregulated in cervical cancer and directly targets FN1 to inhibit cell proliferation and invasion

Oncol Lett. 2019 Aug;18(2):1475-1482. doi: 10.3892/ol.2019.10403. Epub 2019 May 27.


Numerous studies have identified the dysregulation of microRNAs (miRNAs) in cervical cancer, and dysregulated miRNAs are involved in regulating a number of tumour- associated biological behaviours. Therefore, investigating the roles of cervical cancer-associated miRNAs and the underlying molecular mechanisms is essential for the development of novel diagnostic biomarkers and effective therapeutic targets. MicroRNA-432 (miR-432) dysregulation has been revealed to be implicated in the carcinogenesis and progression of a number of types of human cancer. However, the effects and underlying molecular mechanisms of miR-432 in cervical cancer have yet to be elucidated. In the present study, miR-432 expression was determined using reverse transcription-quantitative polymerase chain reaction. The results revealed that miR-432 was expressed at low levels in cervical cancer tissues and cell lines. Decreased miR-432 expression was significantly associated with the International Federation of Gynecology and Obstetrics stage, myometrium invasion and lymph node metastasis of patients with cervical cancer. Following transfection with miR-432 mimic, the expression of miR-432 was significantly upregulated in cervical cancer cells. Upregulation of miR-432 expression restricted the proliferation and invasion of cervical cancer cells. Bioinformatics analysis followed by luciferase reporter assays revealed that fibronectin 1 (FN1) was a direct target gene of miR-432 in cervical cancer cells. In addition, FN1 was upregulated in cervical cancer tissues and was inversely correlated with miR-432 levels. Furthermore, miR-432 upregulation decreased the expression levels of FN1 in cervical cancer cells at the mRNA and protein levels. Furthermore, silencing of FN1 could stimulate the tumour suppressor effects of miR-432 upregulation in cervical cancer cells. In addition, restored FN1 expression neutralized the effects of miR-432 overexpression in cervical cancer cells. The results of the present study indicate that miR-432 is a tumour suppressor that can restrain the aggressive phenotype of cervical cancer cells by directly targeting FN1, suggesting that this miRNA may be developed as an effective therapeutic strategy for patients with cervical cancer.

Keywords: cervical cancer; fibronectin 1; invasion; microRNA-432; proliferation.