Knockdown of TMED3 inhibits cell viability and migration and increases apoptosis in human chordoma cells

Abstract

Chordoma is a rare low-grade tumor of the axial skeleton. Over previous decades, a range of targeted drugs have been used for treating chordoma, with more specific and effective therapies under investigation. Transmembrane Emp24 protein transport domain containing 3 (TMED3) is a novel gene reported to be a regulator of oncogenesis, cancer development and metastasis; however, its role in chordoma remains unclear. In the present study, the expression of TMED3 was investigated in chordoma cells, and the effect of TMED3 knockdown on chordoma development was examined in vitro and in vivo, followed by exploration of differentially expressed proteins in TMED3-silenced chordoma cells via an apoptosis antibody array. Reverse transcription-quantitative PCR and western blot assays were performed to determine the expression levels. It was revealed that TMED3 was highly expressed in chordoma, and that knockdown of TMED3 inhibited cell viability and migration, and enhanced the apoptosis of chordoma cells. Additionally, knockdown of TMED3 inhibited the expression of Bcl-2, heat shock protein 27, insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein-2, Livin, Akt, CDK6 and cyclin D1 proteins, whereas MAPK9 was upregulated. Furthermore, a xenograft nude mice model demonstrated that TMED3 expression promoted tumor growth. Collectively, the present findings suggested that knockdown of TMED3 inhibited cell viability and migration, and enhanced apoptosis in chordoma cells, and that TMED3 may be a novel target for chordoma therapy.