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

IF 4.4 4区医学 Q2 ONCOLOGY Cancer Biology & Therapy Pub Date : 2024-12-31 Epub Date: 2024-03-17 DOI:10.1080/15384047.2024.2329372

Shufeng Liu, Xiaoguang Chen, Liqi Zhang, Bo Lu

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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.

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CPT1A 介导 SP5 的琥珀酰化，SP5 激活 PDPK1 的转录，从而促进前列腺癌细胞的活力和糖酵解。

琥珀酰化修饰涉及人类癌症的进展。本研究旨在探讨琥珀酰基转移酶 CPT1A 在前列腺癌（PCa）进展过程中的作用。CCK-8用于检测细胞活力。海马试验用于评估细胞糖酵解。荧光素酶测定用于检测转录调控。ChIP 用于评估转录因子与启动子之间的结合。Co-IP 用于评估蛋白质之间的结合。我们发现 CPT1A 在 PCa 组织和细胞系中高表达。沉默CPT1A可抑制PCa细胞的活力和糖酵解。从机制上讲，CPT1A 促进了 SP5 的琥珀酰化，从而加强了 SP5 与 PDPK1 启动子的结合。SP5 激活了 PDPK1 的转录，而 PDPK1 激活了 AKT/mTOR 信号通路。这些发现可能会为前列腺癌的诊断或治疗提供新的靶点。

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来源期刊

Cancer Biology & Therapy 医学-肿瘤学

CiteScore

7.00

自引率

0.00%

发文量

审稿时长

2.3 months

期刊介绍： Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.