SHMT2 promotes the tumorigenesis of renal cell carcinoma by regulating the m6A modification of PPAT.
Genomics
; 114(4): 110424, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-35798250
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Glicina Hidroximetiltransferase
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Carcinoma de Células Renais
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Amidofosforribosiltransferase
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Neoplasias Renais
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article