CPT1A mediates the succinylation of SP5 which activates transcription of PDPK1 to promote the viability and glycolysis of prostate cancer cells

Sep 21, 2026

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Succinylation modification influences cancer progression, and this study investigates CPT1A as a succinyltransferase in prostate cancer (PCa). Cell viability was measured using CCK-8, while glycolysis was evaluated with Seahorse assays. Luciferase reporter analysis assessed transcriptional regulation, and ChIP determined promoter-associated binding of transcription factors; Co-IP evaluated protein interactions. CPT1A was highly expressed in PCa tissues and cell lines, and CPT1A silencing suppressed viability and glycolysis. Mechanistically, CPT1A promoted SP5 succinylation, strengthening SP5–PDPK1 promoter binding, driving PDPK1 transcription and AKT/mTOR signaling.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages10

Reading Time25 min

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Abstract

Introduction

Background on prostate cancer and treatment limitations

Role of fatty acid synthesis and succinylation in cancers

Function of CPT1 and rationale for studying CPT1A in PCa

Materials and methods

Tissue specimens

Article information

Dates, correspondence, and publication license

RESEARCH PAPER CPT1A mediates the succinylation of SP5 which activates transcription of PDPK1 to promote the viability and glycolysis of prostate cancer cells Shufeng Liua, Xiaoguang Chenb, Liqi Zhangc, and Bo Lu c aMedical Department, Xiangyang Integrated Traditional and Western Medicine Hospital, Xiangyang, Hubei, China; bUrology Department, Xiangyang Integrated Traditional and Western Medicine Hospital, Xiangyang, Hubei, China; cLaboratory Department, Xiangyang Integrated Traditional and Western Medicine Hospital, Xiangyang, Hubei, China ABSTRACT Succinylation modification involves in the progression of human cancers. The present study aimed to investigate the role of CPT1A, which is a succinyltransferase in the progression of prostate cancer (PCa) . CCK-8 was used to detect the cell viability. Seahorse was performed to evaluate the cell glycolysis. Luciferase assay was used to detect the transcriptional regulation. ChIP was performed to assess the binding between transcriptional factors with the promoters. Co-IP was used to assess the binding between proteins. We found that CPT1A was highly expressed in PCa tissues and cell lines. Silencing of CPT1A inhibited the viability and glycolysis of PCa cells. Mechanistically, CPT1A promoted the succinylation of SP5, which strengthened the binding between SP5 and the promoter of PDPK1 . SP5 activated PDPK1 transcription and PDPK1 activated the AKT/mTOR signal pathway. These findings might provide novel targets for the diagnosis or therapy of prostate cancer. ARTICLE HISTORY Received 25 October 2023 Revised 19 February 2024 Accepted 7 March 2024 KEYWORDS Prostate cancer; CPT1A; SP5; PDPK1; succinylation; transcription Introduction Prostate cancer (PCa) is the third leading cause of cancer related death and is the fifth most common cancer worldwide. 1,2 Although the incidence of PCa is declining, there are still one million new cases worldwide each year.3 The 5-year survival rate of early PCa is more than 60% .4 Surgery and radiation are the curative treatments for localized disease; however, adverse effects seriously affect the quality of life.5 Growing evidence has highlighted the important role of androgen receptors (AR) in the onset and progression of PCa, so androgen deprivation therapy alone is the standard treatment for metastatic PCa.6 Unfortunately, the 5-year survival rate for advanced PCa decreases to 30% .7,8 This suggests that we need to have a deeper understanding of the pathogenesis of PCa and explore new therapeutic strategies. PCa has been found to exhibit high rates of de novo fatty acid synthesis driven by activation of the AR.9 Fatty acid synthesis is a synthetic process whereby two carbons are added in a stepwise manner to a growing chain that can be further modified by addition of substituents on the hydrocarbon chain such as the succinyl group. Increased studies have shown that succinylation modification promotes or inhibits the progression of various cancers by regulating different substrate targets or signaling pathways, such as liver cancer, breast cancer, gastric cancer and PCa. 10–13 However, the modification pathway and regulation mechanisms of succinylation modification in the occurrence and development of PCa remain unknown. Succinylation modification refers to the covalent binding of succinyl groups by succinyl-coenzyme A (CoA) donors to lysine residues, which is a newly discovered post-translational modification of proteins.14, 15 It exists widely in cells and participates in a variety of biological processes. 16 Succinylation is involved in the tricarboxylic acid cycle, amino acid metabolism and fatty acid metabolism by regulating protease activity and gene expression. 17 Therefore, it is of great significance to explore the role of succinylation in PCa. Carnitine palmitoyl transferase 1 (CPT1) controls the ratelimiting step of fatty acid oxidation.18 It promotes the passage of fatty acids into the mitochondria by loading

FAQs

How was CPT1A’s effect on prostate cancer cell viability assessed?

Cell viability was measured using a CCK-8 assay after manipulating CPT1A expression.

What experiments were used to evaluate glycolysis in PCa cells?

Glycolysis was evaluated using Seahorse assays.

What is the proposed molecular mechanism linking CPT1A to PDPK1 transcription?

CPT1A promoted succinylation of SP5, which strengthened SP5 binding to the PDPK1 promoter; SP5 then activated PDPK1 transcription and triggered AKT/mTOR signaling.

Sep 21, 2026

Uploaded by Finn