2. Academic Validation
  3. CPT1A mediates succinylation of LDHA at K318 site promoteing metabolic reprogramming in NK/T-cell lymphoma nasal type

CPT1A mediates succinylation of LDHA at K318 site promoteing metabolic reprogramming in NK/T-cell lymphoma nasal type

  • Cell Biol Toxicol. 2025 Feb 11;41(1):42. doi: 10.1007/s10565-025-09994-6.
Hao Tian 1,  Yi Ge 2,  Jianjun Yu 1,  Xing Chen 1,  Honghan Wang 1,  Xu Cai 1,  Zhenfeng Shan 1,  Liang Zuo 3,  Yan Liu 4
Affiliations

Affiliations

  • 1 Department of Head & Neck Surgery, Hunan Cancer Hospital &, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China.
  • 2 Department of Stomatology, Hengyang Central Hospital, Yanfeng District, No.12, Yancheng Road, Hengyang, 421001, Hunan, China.
  • 3 Department of Head & Neck Surgery, Hunan Cancer Hospital &, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China. zuoliang@hnca.org.cn.
  • 4 Department of Head & Neck Surgery, Hunan Cancer Hospital &, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China. liuyan2758@hnca.org.cn.
PMID: 39934546 DOI: 10.1007/s10565-025-09994-6
Abstract

Carnitine palmitoyltransferase 1A (CPT1A), a succinylating Enzyme, is highly expressed in various malignant tumors and promotes tumor progression. Succinylation is a posttranslational modification that has been reported in various diseases, but its role in NK/T-Cell lymphoma nasal type (ENKTL-NT) remains underexplored. In this study, bioinformatics analysis showed that glycolytic is a major metabolic pathway in ENKTL-NT as the expression of many glycolytic related kinases are increased. CPT1A probably mediates glycolytic process, as indicated by GO-enrichment analysis. Studies showed that CPT1A was upregulated in ENKTL-NT tissues, and that high CPT1A expression was associated with poor prognosis of ENKTL-NT. CPT1A promoted the proliferation, colony formation, invasion and glycolytic process of ENKTL-NT cells and suppresses Apoptosis. Mechanistically, CPT1A promotes succinylation of LDHA at lysine 318 (K318), which increase the protein stability and the final protein level of LDHA. Both knockdown and mutation (K318R) of LDHA abolished the cancer-promoting effects of CPT1A in ENKTL-NT. In all, this study reveals the mechanism underlying the cancer-promoting effects of CPT1A via inducing LDHA succinylation and metabolic reprogramming in ENKTL-NT. These findings might provide potential targets for the diagnosis or therapy of ENKTL-NT.

Keywords

CPT1A; ENKTL-NT; Glycolytic; LDHA; Metabolic reprogramming; Succinylation.

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