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
  • 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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