目的  探讨跨膜蛋白158 （TMEM158）调控骨肉瘤进展的机制，寻找临床干预的潜在靶点。 方法  通过对基因表达综合数据库（GEO）数据集的生物信息学分析表明TMEM158高表达与骨肉瘤预后不良相关。RNA测序分析显示，TMEM158敲低组的下调基因富集于Notch信号通路。通过Western blotting，Real-time PCR，CCK-8，划痕实验和transwell实验，研究敲低TMEM158及Notch受体激动剂Jagged-1（188-204，TFA）处理对143B骨肉瘤细胞增殖、迁移和侵袭的影响。 结果  生物信息学分析和实验验证显示，TMEM158在骨肉瘤组织和143B细胞中表达升高。细胞实验显示，在143B细胞中敲低TMEM158可显著降低细胞的增殖、侵袭和迁移能力，Jagged-1处理可有效逆转敲低TMEM158对143B细胞功能表型的抑制作用。 结论  TMEM158可通过调控Notch信号通路促进骨肉瘤进展，TMEM158有望成为骨肉瘤治疗的潜在靶点。

Objective  To investigate the mechanism by which transmembrane protein 158 (TMEM158) regulates osteosarcoma progression and to identify potential targets for clinical intervention.  Methods  Bioinformatics analysis of the Gene Expression Omnibus(GEO) datasets indicated that high expression of TMEM158 was associated with poor prognosis in patients with osteosarcoma. RNA sequencing analysis revealed that the downregulated genes in the TMEM158 knockdown group were enriched in the Notch signaling pathway.Western blotting,Real-time PCR,CCK-8 assay,wound healing assay, and transwell assay were performed to evaluate the effects of TMEM158 knockdown and treatment with Jagged-1(188-204, TFA, an agonist of Notch receptor)on the proliferation, migration, and invasion of 143B osteosarcoma cells.  Results  Bioinformatics analysis and experimental validation revealed elevated expression of TMEM158 in both osteosarcoma tissue and 143B cells. Cellular experiments demonstrated that knockdown of TMEM158 in 143B cells significantly inhibited cell proliferation, invasion, and migration. Treatment with Jagged-1 effectively reversed the inhibitory effects of TMEM158 knockdown on 143B cell phenotypes.   Conclusion  TMEM158 may promote the progression of osteosarcoma by regulating the Notch signaling pathway, and could serve as a potential therapeutic target for osteosarcoma.