miR-144 inhibits growth and metastasis of cervical cancer cells by targeting VEGFA and VEGFC

Exp Ther Med. 2018 Jan;15(1):562-568. doi: 10.3892/etm.2017.5392. Epub 2017 Oct 30.

Abstract

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.

Keywords: cervical cancer; microRNA-144; microRNAs; suppressor; vascular endothelial growth factor A; vascular endothelial growth factor C.