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

Genomics

Department of Pathology, Xuzhou Medical University, 209 Tong-shan Road, Xuzhou, Jiangsu, China. Electronic address:

Published: July 2022

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygeno.2022.110424DOI Listing

Publication Analysis

Top Keywords

shmt2
12
shmt2 promotes
8
renal cell
8
cell carcinoma
8
m6a modification
8
rcc cell
8
cell proliferation
8
shmt2 promoted
8
ppat expression
8
ppat
6

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!