Table_3_Overexpression of SHMT2 Predicts a Poor Prognosis and Promotes Tumor Cell Growth in Bladder Cancer.DOCX

SHMT2 was overexpressed in many tumors, however, the role of SHMT2 in bladder cancer (BLCA) remains unclear. We first analyzed the expression pattern of SHMT2 in BLCA using the TNMplot, Oncomine, the Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) databases. Next, the association between SHMT2 expression and overall survival (OS)/disease-free survival (DFS) in BLCA patients were analyzed using TCGA and PrognoScan database. The correlation between SHMT2 expression and clinicopathology was determined using TCGA database. Furthermore, the genes co-expressed with SHMT2 and their underlying molecular function in BLCA were explored based on the Oncomine database, Metascape and gene set enrichment analysis (GSEA). Finally, the effects of SHMT2 on cell proliferation, cell cycle, and apoptosis were assessed using in vitro experiments. As a results, SHMT2 was significantly overexpressed in BLCA tissues and cells compared to normal bladder tissues and cells. A high SHMT2 expression predicts a poor OS of BLCA patients. In addition, SHMT2 expression was higher in patients with a high tumor grade and in those who were older than 60 years. However, the expression of SHMT2 was not correlated with gender, tumor stage, lymph node stage, and distant metastasis stage. Finally, overexpression of SHMT2 promoted BLCA cell proliferation and suppressed apoptosis, the silencing of SHMT2 significantly inhibited BLCA cell proliferation by impairing the cell cycle, and promoting apoptosis. SHMT2 mediates BLCA cells growth by regulating STAT3 signaling. In summary, SHMT2 regulates the proliferation, cell cycle and apoptosis of BLCA cells, and may act as a candidate therapeutic target for BLCA.

SHMT2在众多肿瘤中呈过表达状态，然而其在膀胱癌（BLCA）中的作用尚不明确。本研究首先利用TNMplot、Oncomine、癌症基因组图谱（TCGA）以及基因表达综合数据库（GEO）等，分析了SHMT2在BLCA中的表达模式。随后，通过TCGA和PrognoScan数据库，探讨了SHMT2表达与BLCA患者总生存期（OS）/无病生存期（DFS）之间的关联。利用TCGA数据库确定了SHMT2表达与临床病理特征之间的相关性。进一步地，基于Oncomine数据库、Metascape以及基因集富集分析（GSEA），探讨了与SHMT2共表达的基因及其在BLCA中的潜在分子功能。最后，通过体外实验评估了SHMT2对细胞增殖、细胞周期和凋亡的影响。结果表明，与正常膀胱组织细胞相比，SHMT2在BLCA组织和细胞中显著过表达。高水平的SHMT2表达预示着BLCA患者预后不良。此外，SHMT2表达在肿瘤分级较高和年龄超过60岁的患者中较高。然而，SHMT2的表达与性别、肿瘤分期、淋巴结分期以及远处转移分期无显著相关性。最终，SHMT2的过表达促进了BLCA细胞的增殖并抑制了细胞凋亡，而SHMT2的沉默通过干扰细胞周期并促进细胞凋亡，显著抑制了BLCA细胞的增殖。SHMT2通过调节STAT3信号通路介导BLCA细胞的生长。总之，SHMT2调控BLCA细胞的增殖、细胞周期和凋亡，可能成为BLCA的潜在治疗靶点。