MiR-27a inhibits cervical adenocarcinoma progression by downregulating the TGF-?RI signaling pathway.

ABSTRACT: High-risk human papillomavirus infection is essential for the malignant transformation of cervical cancer and can inhibit host miR-27a expression. We investigated the role and mechanism of miR-27a in cervical cancer progression. miR-27a is decreased in cervical cancer cell lines and miR-27a-agomir inhibited the cell proliferation, migration, and invasion properties of HeLa (adenocarcinoma) cells, but not in SiHa cells (squamous cell carcinoma). Luciferase assays revealed that miR-27a directly targets the 3'-UTR of transforming growth factor beta receptor I (TGF-?RI) and downregulates TGF-? signaling. The co-transfection of a TGF-?RI expression vector largely restored the inhibition of TGF-? signaling, cell proliferation, migration, and invasion mediated by miR-27a-agomir. Also, miR-27a-agomir slows down the growth of subcutaneous HeLa xenografts and downregulates the TGF-?RI expression and TGF-? signaling in tumor in vivo. Tissue microarray analysis revealed a low miR-27a level in adenocarcinoma cells, but not in squamous cell carcinoma cells, which was negatively associated with TGF-?RI expression. High TGF-?RI correlated with deep stromal invasion and lymph node metastasis. These results suggest that miR-27a acts as a tumor suppressor in cervical cancer, especially in adenocarcinoma, by inhibiting TGF-?RI signaling pathway. Thus, enhancing miR-27a expression and function may be a novel treatment strategy for cervical adenocarcinoma.

SUBMITTER: Fang F 

PROVIDER: S-EPMC5847584 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature