2. Academic Validation
  3. SHMT2 promotes the tumorigenesis of renal cell carcinoma by regulating the m6A modification of PPAT

SHMT2 promotes the tumorigenesis of renal cell carcinoma by regulating the m6A modification of PPAT

  • Genomics. 2022 Jul;114(4):110424. doi: 10.1016/j.ygeno.2022.110424.
Fu-Chun Huo 1,  Min Xie 2,  Zhi-Man Zhu 3,  Jun-Nian Zheng 4,  Dong-Sheng Pei 5
Affiliations

Affiliations

  • 1 Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Pathology, Xuzhou Medical University, 209 Tong-shan Road, Xuzhou, Jiangsu, China.
  • 2 Department of Pathology, Taizhou People's Hospital, 366 Taihu Road, Taizhou, Jiangsu, China.
  • 3 Department of Pathology, Xuzhou Medical University, 209 Tong-shan Road, Xuzhou, Jiangsu, China.
  • 4 Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Center of Clinical Oncology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address: [email protected].
  • 5 Department of Pathology, Xuzhou Medical University, 209 Tong-shan Road, Xuzhou, Jiangsu, China. Electronic address: [email protected].
PMID: 35798250 DOI: 10.1016/j.ygeno.2022.110424
Abstract

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.

Keywords

Metabolism; N6-methyladenosine; PPAT; Renal cell carcinoma; SHMT2.

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