SHMT2 通过调节 PPAT 的 m6A 修饰促进肾细胞癌的发生。
SHMT2 promotes the tumorigenesis of renal cell carcinoma by regulating the m6A modification of PPAT.
机构信息
Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Pathology, Xuzhou Medical University, 209 Tong-shan Road, Xuzhou, Jiangsu, China.
Department of Pathology, Taizhou People's Hospital, 366 Taihu Road, Taizhou, Jiangsu, China.
出版信息
Genomics. 2022 Jul;114(4):110424. doi: 10.1016/j.ygeno.2022.110424. Epub 2022 Jul 5.
OBJECTIVE
Serine hydroxymethyltransferase 2 (SHMT2) is the first rate-limiting enzyme for serine/glycine biosynthesis and one carbon metabolism. Here, we explore the underlying mechanism of how SHMT2 functions in renal cell carcinoma (RCC) initiation.
METHODS
In this study, SHMT2 expression was assessed in RCC tissues. In vitro experiments were performed to investigate the functional role of SHMT2. The detailed mechanisms of SHMT2-mediated PPAT were addressed.
RESULTS
Increased SHMT2 facilitated RCC cell proliferation by inducing the G1/S phase transition. And SHMT2 promoted the expression of PPAT. Mechanism dissection revealed that SHMT2 enhanced the m6A modification through the endogenous methyl donor SAM mediated by SHMT2 via serine/glycine one carbon metabolic networks. SHMT2-catalyzed serine/glycine conversion regulated PPAT expression in an m6A-IGF2BP2-dependent manner. SHMT2 promoted RCC cell proliferation by upregulating PPAT expression.
CONCLUSIONS
SHMT2 promotes RCC tumorigenesis by increasing PPAT expression. Thus, SHMT2 may be a novel potential therapeutic target for RCC.
目的
丝氨酸羟甲基转移酶 2（SHMT2）是丝氨酸/甘氨酸生物合成和一碳代谢的第一个限速酶。在这里，我们探讨了 SHMT2 在肾细胞癌（RCC）发生中的作用机制。
方法
本研究评估了 SHMT2 在 RCC 组织中的表达。进行了体外实验以研究 SHMT2 的功能作用。探讨了 SHMT2 介导的 PPAT 的详细机制。
结果
增加的 SHMT2 通过诱导 G1/S 期转变促进 RCC 细胞增殖。并且 SHMT2 促进了 PPAT 的表达。机制剖析显示，SHMT2 通过 SHMT2 通过丝氨酸/甘氨酸一碳代谢网络介导的内源性甲基供体 SAM 增强了 m6A 修饰。SHMT2 催化的丝氨酸/甘氨酸转化以依赖 m6A-IGF2BP2 的方式调节 PPAT 的表达。SHMT2 通过上调 PPAT 表达促进 RCC 细胞增殖。
结论
SHMT2 通过增加 PPAT 的表达促进 RCC 肿瘤发生。因此，SHMT2 可能是 RCC 的一种新的潜在治疗靶点。
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