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.
[1]Peoples Hosp Shanghai Pudong New Area, Dept Obstet & Gynecol, Shanghai 201299, Peoples R China.
[2]Fudan Univ, Dept Gynecol Oncol, Shanghai Canc Ctr, 270 Dongan Rd, Shanghai 200032, Peoples R China.
[3]Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China.
[4]Peoples Hosp Shanghai Pudong New Area, Dept Pathol, Shanghai 201299, Peoples R China.
(8.0+极速模式)