Osteosarcoma is suggested to be caused by genetic and molecular alterations that disrupt osteoblast differentiation. Recent studies have reported that transmembrane
protein 119 (TMEM119) contributes to osteoblast differentiation and bone development. However, the level of TMEM119 expression and its roles in
osteosarcoma have not yet been elucidated. In the present study, TMEM119
mRNA and
protein expression was found to be up-regulated in
osteosarcoma compared with normal
bone cyst tissues. The level of TMEM119
protein expression was strongly associated with
tumor size, clinical stage, distant
metastasis and overall survival time. Moreover, gene set enrichment analysis (GSEA) of the Gene Expression Omnibus (GEO) GSE42352 dataset revealed TMEM119 expression in
osteosarcoma tissues to be positively correlated with cell cycle, apoptosis,
metastasis and TGF-β signaling. We then knocked down TMEM119 expression in U2OS and MG63 cells using
small interfering RNA, which revealed that downregulation of TMEM119 could inhibit the proliferation of
osteosarcoma cells by inducing cell cycle arrest in G0/G1 phase and apoptosis. We also found that TMEM119 knockdown significantly inhibited cell migration and invasion, and decreased the expression of TGF-β pathway-related factors (BMP2, BMP7 and TGF-β). TGF-β application rescued the inhibitory effects of TMEM119 knockdown on
osteosarcoma cell migration and invasion. Further in vitro experiments with a TGF-β inhibitor (
SB431542) or BMP inhibitor (
dorsomorphin) suggested that TMEM119 significantly promotes cell migration and invasion, partly through TGF-β/BMP signaling. In conclusion, our data support the notion that TMEM119 contributes to the proliferation, migration and invasion of
osteosarcoma cells, and functions as an oncogene in
osteosarcoma.