Upregulation and biological function of transmembrane protein 119 in osteosarcoma

Abstract

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.

TMEM119 promotes gastric cancer cell migration and invasion through STAT3 signaling pathway

“… 33 However, evidence on the function of TMEM119 in tumorigenesis, especially cell migration and invasion, was extremely limited. Only Jiang et al 19 showed that TMEM119 silencing contributed to decreased migration and invasion of osteosarcoma cells and expression of metastasis-related proteins (MMP2, N-cadherin, E-cadherin, Vimentin, and Twist1), which in part agree with our findings that TMEM119 enhanced invasion and migration of gastric cancer cells as well as the MMP2 and MMP9 expression.…”

“…In line with our findings, some studies showed that TMEM119 was overexpressed in osteosarcoma, benign phyllodes tumors of the breast, and prostate cancer. 16 , 17 , 19 However, downregulated TMEM119 expression was observed in oral squamous cell carcinoma. 18 These results suggest that the expression pattern is different in different cancers.…”

“… 18 Moreover, TMEM119 was highly expressed in osteosarcoma, was associated with poor survival of osteosarcoma patients, and promoted osteosarcoma cell migration and invasion through TGF-β/BMP signaling. 19 However, the functions of TMEM119 in gastric cancer still need to be explored.…”

CXCR4‐mediated osteosarcoma growth and pulmonary metastasis is suppressed by MicroRNA‐613

“…Studies have demonstrated that osteosarcoma may be involved in genetic and molecular alterations which affect osteoblast differentiation. 14,15 SDF-1/CXCR4 axis was found to play important roles in almost all malignancies including osteosarcoma. 16,17 miRNAs play critical roles in regulating cell processes and may function as oncogenes or tumor suppressors to regulate gene and protein expression.…”

Myeloid Cells in Multiple Sclerosis

“…Both P2RY12 and TMEM119 are expressed by the vast majority of microglia within the healthy CNS. The function of TMEM119 in microglia has not been yet elucidated, but in other cell types, it has been implicated with differentiation and proliferation [39][40][41][42]. P2RY12 serves as a chemotactic receptor that guides microglia to sites of injury [26].…”