SHMT2 Drives the Progression of Colorectal Cancer by Regulating UHRF1 Expression.
SHMT2 Drives the Progression of Colorectal Cancer by Regulating UHRF1 Expression.
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SHMT2通过调节UHRF1表达驱动结直肠癌的进展
DOI：
10.1155/2022/3758697
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发表时间：
2022
影响因子：
2.7
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Cui X;Cui Y;Du T;Jiang X;Song C;Zhang S;Ma C;Liu Y;Ni Q;Gao Y;Wang G
前言丝氨酸羟甲基转移酶2(SHMT2)在丝氨酸-甘氨酸代谢中起关键作用，从而驱动癌细胞的增殖。然而，SHMT2在肿瘤发生中的作用，特别是在人类结直肠癌(CRC)进展中的作用，仍然很大程度上不清楚。材料与方法收集上海交通大学医学院新华医院结直肠外科手术标本，采用实时定量聚合酶链式反应(QPCR)、免疫印迹(WB)和免疫组织化学(IHC)方法进行检测。用定量聚合酶链式反应和免疫印迹法检测SHMT2在人结直肠癌细胞中的表达。通过体外和体内实验研究SHMT2基因敲除后对结直肠癌细胞的增殖、迁移和侵袭的影响。用mRNA-序列分析来研究SHMT2功能背后的潜在机制。结果SHMT2mRNA和蛋白在结直肠癌组织中的表达明显高于正常组织。SHMT2的阳性表达与结直肠癌的TNM分期和淋巴结转移密切相关，SHMT2的高表达是影响结直肠癌患者预后的独立因素。SHMT2基因敲除可抑制结直肠癌细胞在体内外的增殖，并通过调节uhrf1的表达诱导细胞周期停滞。结论uhrf1是SHMT2的一个新的靶基因，有望成为治疗结直肠癌的新靶点。
Introduction Serine hydroxymethyltransferase 2 (SHMT2) has a critical role in serine-glycine metabolism to drive cancer cell proliferation. Yet, the function of SHMT2 in tumorigenesis, especially in human colorectal cancer (CRC) progression, remains largely unclear. Materials and Methods CRC and paired normal samples were collected in the Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, and assessed by real-time polymerase chain reaction (qPCR) analysis, western blot (WB), and immunohistochemistry (IHC). Moreover, SHMT2 expression in human CRC cells was identified by qPCR and WB. The CRC cell proliferation, migration, and invasion after SHMT2 knockdown were explored through in vitro and in vivo assays. mRNA-seq assays were used to investigate the underlying mechanisms behind the SHMT2 function. Results It was found that SHMT2 mRNA and protein were overexpressed in CRC tissue compared to the levels in normal mucosa. Positive expression of SHMT2 was significantly correlated with TNM stage and lymph node metastasis, and elevated expression of SHMT2 resulted as an independent prognostic factor in patients with CRC. SHMT2 knockdown impaired the proliferation of CRC in vitro and in vivo and induced cell cycle arrest by regulating UHRF1 expression. Conclusion Taken together, our findings reveal that UHRF1 is a novel target gene of SHMT2, which can be used as a potential therapeutic strategy for CRC therapy.
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