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

摘要

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'untrans-lated 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.