Upregulation and biological function of transmembrane protein 119 in osteosarcoma

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.

Association between IL-10 gene polymorphisms and the outcomes of hepatitis C virus infection among high-risk populations in Jiangsu province / 中华流行病学杂志

Objective To explore the relationship between interleukin (IL)-10 gene polymorphisms and the susceptibility or the outcomes of HCV infection among high-risk populations in Jiangsu province.Methods IL-10 gene SNPs were detected in 1555 subjects including 264 self-limited HCV infections.371 persistent HCV infections and 920 healthy controls were selected through Taqman-MGB.Results After adjusted for cofounders as sex,age and high-risk population,data from logistic regression analysis showed that the distribution of IL-10 genotypes among the controls,spontaneous clearances and those with persistent infections did not show much differences.Results from further stratified analysis showed that,at the position of-819T/C,when compared with TT genotype,TC genotype had a significantly increasing chance of self-limited HCV infection among middle-aged,females and paid blood doners (adjusted OR values and 95％ CI were:2.160,1.163 4.011 ；1.693,1.066-2.688 and 4.084,1.743-9.570).It also had a lower risk of progressing to persistent HCV infection among those paid blood doners (the adjusted OR values and 95％CI were:0.312,0.130-0.747 ).CC genotype had a higher chance of self-limited HCV infection among people underwent blood dialysis (the adjusted OR values and 95％CI were:2.120,1.071 -4.197).Results also showed a decreased risk of progressing to persistent infection among paid blood doners (the adjusted OR values and 95％CI were:0.156,0.043-0.566).At the position of -592A/C,when compared to AA genotypc,the AC genotype had a significantly increasing chance of self-limited HCV infection among middle-aged,femalcs and paid blood doners (the adjusted OR values and 95％ CI were:2.176,1.173-4.037；1.659,1.055-2.607;3.704,1.625-8.443) but had an increased risk of persistent HCV infection among females (the adjusted OR values and 95％CI were:1.525,1.017-2.286).AC genotype showed an increased opportunity to progress to HCV persistent infection among drug users (the adjusted OR values and 95％CI were:1.845,1.122-3.034) but had a reduced risk of progressing to HCV persistent infection among paid blood doners (the adjusted OR values and 95％CI were:0.361,0.155-0.841 ).CC genotype had an increased opportunity to self-linited HCV infection as well as having a dccreased risk of progressing to persistent infection among paid blood donets (the adjusted OR values and 95％CI were:3.125,1.016-9.605；0.218,0.063-0.748).At the position of-1082A/G,AG/GG genotypcs had an increased chance of self-limited infection among blood doners (the adjusted OR values and 95％CI were:3.780,1.620-8.820).Conclusion IL-10-819T/C,-592A/C,-1082A/G SNPs might be related with the susceptibility and the outcomes of HCV infection among populations at high risk.