Downregulation of microRNA-205 inhibits cell invasion and angiogenesis of cervical cancer through TSLC1-mediated Akt signaling pathway.

Abstract

Cervical cancer (CC) is a common gynecological cancer and a leading cause of cancer-related deaths in women globally. Therefore, this study explores the action of microRNA-205 (miR-205) in the invasion, migration, and angiogenesis of CC through binding to tumor suppressor lung cancer 1 (TSLC1). Initially, the microarray analysis was used to select the candidate gene and the regulatory microRNA. Then, the target relationship between miR-205 and TSLC1 as well as the expression of miR-205, TSLC1, and p-Akt/total Akt in CC cells were determined. Afterwards, CC cell invasion and migration were detected after the treatment of miR-205 mimics/inhibitors and short hairpin RNA against TSLC1. After coculture of cancer cells and vascular endothelial cells, cell proliferation, tube formation, and microvessel density (MVD) were detected to determine the roles of miR-205 in angiogenesis. Finally, tumor growth in nude mice was measured in vivo. TSLC1 was determined as the candidate gene, which was found to be targeted and negatively regulated by miR-205. Then, downregulated miR-205 or forced TSLC1 expression inhibited invasion, migration, and angiogenesis in CC, corresponding to suppressed cell proliferation, tube formation, and expression of IL-8, VEGF, and bFGF, as well as the inhibited activation of the Akt signaling pathway. Furthermore, downregulation of miR-205 was found to exert an inhibitory role in tumor formation and MVD by elevating TSLC1 in CC in vivo. This study demonstrated that downregulated miR-205 inhibited cell invasion, migration, and angiogenesis in CC by inactivating the Akt signaling pathway via TSLC1 upregulation.