Department of Gastrointestinal Surgery, Shanghai East Hospital (East Hospital Affiliated to Tongji University), Shanghai 200092, China.
Department of Radiology, Shanxi Province Cancer Hospital, Shanxi Medical University, Taiyuan 030013, China.
Can J Gastroenterol Hepatol. 2022 Feb 15;2022:3758697. doi: 10.1155/2022/3758697. eCollection 2022.
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.
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 and assays. mRNA-seq assays were used to investigate the underlying mechanisms behind the SHMT2 function.
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 and and induced cell cycle arrest by regulating UHRF1 expression.
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.
丝氨酸羟甲基转移酶 2（SHMT2）在丝氨酸-甘氨酸代谢中发挥关键作用，以促进癌细胞增殖。然而，SHMT2 在肿瘤发生中的作用，尤其是在人类结直肠癌（CRC）进展中的作用，在很大程度上仍不清楚。
在上海交通大学医学院新华医院普外科收集 CRC 及配对的正常样本，并通过实时聚合酶链反应（qPCR）分析、western blot（WB）和免疫组织化学（IHC）进行评估。此外，通过 qPCR 和 WB 鉴定了人 CRC 细胞中的 SHMT2 表达。通过 和 检测 SHMT2 敲低后 CRC 细胞的增殖、迁移和侵袭。使用 mRNA-seq 检测来研究 SHMT2 功能背后的潜在机制。
研究发现，与正常黏膜相比，CRC 组织中 SHMT2 mRNA 和蛋白表达过度。SHMT2 的阳性表达与 TNM 分期和淋巴结转移显著相关，并且在 CRC 患者中，高表达 SHMT2 是独立的预后因素。SHMT2 敲低可通过调节 UHRF1 表达，抑制 CRC 的增殖、和 ，并诱导细胞周期停滞。
总之，我们的研究结果表明，UHRF1 是 SHMT2 的一个新的靶基因，可以作为 CRC 治疗的潜在治疗策略。
