Inhibitory roles of miR-9 on papillary thyroid cancer through targeting BRAF

Abstract

MicroRNA-9 (miR-9) is reported to be underex-pressed in papillary thyroid carcinoma (PTC) tissues; however, the molecular mechanisms underlying the implication of miR-9 in PTC have yet to be elucidated. The present study aimed to explore the potential roles of miR-9 in PTC. PTC tissue samples and paired non-cancerous adjacent tissues were collected from 60 patients with PTC. The human TPC-1 thyroid gland papillary carcinoma cell line was used to investigate the molecular mechanisms underlying the roles of miR-9 in PTC. The levels of miR-9 and its downstream target gene BRAF were detected through reverse transcription-quantitative polymerase chain reaction. MTT assay and flow cytometry were performed to evaluate cell viability and apoptosis, respectively. A mouse xenograft tumor model was established to observe the effects of miR-9 on thyroid gland tumorigenesis in vivo. The present study revealed that the expression of miR-9 was significantly reduced in PTC tissues compared with paired normal tissues. In addition, miR-9 upregulation suppressed the expression of BRAF in TPC-1 cells in vitro. Luciferase reporter assay demonstrated that BRAF may be a direct target gene of miR-9 in TPC-1 cells. In addition, following transfection with miR-9 mimics, the viability of TPC-1 cells was suppressed and their apoptosis was enhanced; conversely, transfection with miR-9 inhibitor exerted the opposite effects in vitro. miR-9 overexpression or downregulation also affected in vivo PTC tumorigenesis in athymic mice. The present findings suggested that miR-9 may suppress the viability of PTC cells and inhibit tumor growth through directly targeting the expression of BRAF in PTC.