Bone Marrow Mesenchymal Stem Cells (BMSCs)-Triggered Up-Regulation of miR-198 Impedes the Aggressive Migration and Invasion of Cervical Cancer Cells

Abstract

As a subset of RNAs without protein-coding function, short non-coding RNAs (microRNAs) are reported to contribute to the progress of multiple disorders. Nevertheless, the precise function of miR-198 in human cervical cancer is still an open question. RNA sequencing between cervical cancer cell lines and normal cervical epithelial cells identified CCAR1 to be highly expressed in cervical cancer. Cells were transfected with si-CCAR1 followed by analysis of cell behaviors using clonogenic assay and transwell migrating assay. The binding of miR-198 and CCAR1 was verified by a dual-luciferase reporter gene experiment. CCAR1 was highly expressed in cervical cancer tissues and cell lines and associated with tumor staging. Knockdown of CCAR1 restrained the malignant phenotypes of cervical cancer cells. CCAR1 was a target of miR198. Co-culture with BMSCs upregulated miR-198 expression, resulting in impediment of the aggressive phenotypes of cervical cancer cells, which was mediated by suppression of CCAR1 and release of inflammatory factors. In conclusion, CCAR1 level is increased in cervical cancer tissues or cell lines. Co-culture of BMSCs can facilitate the proliferating, migrating and invading activities of cervical cancer cells but reduce the release of inflammatory factors which is possibly through manipulating the axis of miR-198/CCAR1.