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RNF4介导的PDHA1降解促进结直肠癌的代谢和转移。

RNF4 mediated degradation of PDHA1 promotes colorectal cancer metabolism and metastasis.

作者信息

Chen Jierong, Li Zi-Yue, Zheng Guansheng, Cao Lixue, Guo Yun-Miao, Lian Qizhou, Gu Bing, Yue Cai-Feng

机构信息

Department of Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, PR China.

Cord Blood Bank, Guangzhou Institute of Eugenics and Perinatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510000, PR China.

出版信息

NPJ Precis Oncol. 2024 Nov 9;8(1):258. doi: 10.1038/s41698-024-00724-5.

DOI:10.1038/s41698-024-00724-5
PMID:39521913
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11550450/
Abstract

This study investigates the role of RNF4-mediated ubiquitination and degradation of PDHA1 in colorectal cancer (CRC) metabolism and metastasis. Integrating (The Cancer Genome Atlas) TCGA and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, proteomic, clinical, and metabolomic analyses were performed, revealing PDHA1 as a prognostic marker in CRC. Immunohistochemical staining confirmed lower PDHA1 expression in metastatic CRC tissues. In vitro experiments demonstrated that PDHA1 overexpression inhibited CRC cell proliferation, migration, and invasion. RNF4 was identified as a key mediator in the ubiquitination degradation of PDHA1, influencing glycolytic pathways in CRC cells. Metabolomic analysis of serum samples from metastatic CRC patients further supported these findings. In vivo experiments, including xenograft and metastasis models, validated that RNF4 knockdown stabilized PDHA1, inhibiting tumor formation and metastasis. This study highlights the critical role of RNF4-mediated PDHA1 ubiquitination in promoting glycolytic metabolism, proliferation, and metastasis in CRC.

摘要

本研究调查了RNF4介导的PDHA1泛素化和降解在结直肠癌（CRC）代谢和转移中的作用。整合癌症基因组图谱（TCGA）和临床蛋白质组肿瘤分析联盟（CPTAC）数据库，进行了蛋白质组学、临床和代谢组学分析，揭示PDHA1是CRC的一个预后标志物。免疫组织化学染色证实转移性CRC组织中PDHA1表达较低。体外实验表明，PDHA1过表达抑制CRC细胞增殖、迁移和侵袭。RNF4被确定为PDHA1泛素化降解的关键介质，影响CRC细胞中的糖酵解途径。对转移性CRC患者血清样本的代谢组学分析进一步支持了这些发现。体内实验，包括异种移植和转移模型，证实RNF4敲低可稳定PDHA1，抑制肿瘤形成和转移。本研究强调了RNF4介导的PDHA1泛素化在促进CRC糖酵解代谢、增殖和转移中的关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab94/11550450/943314219070/41698_2024_724_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab94/11550450/451d94ebde0f/41698_2024_724_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab94/11550450/2d1d35bb3e50/41698_2024_724_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab94/11550450/943314219070/41698_2024_724_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab94/11550450/11e3c360676d/41698_2024_724_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab94/11550450/6652f6d4cadf/41698_2024_724_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab94/11550450/761c2b093230/41698_2024_724_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab94/11550450/2da9d41023d9/41698_2024_724_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab94/11550450/75533aa9f04d/41698_2024_724_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab94/11550450/33b2d0555955/41698_2024_724_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab94/11550450/451d94ebde0f/41698_2024_724_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab94/11550450/2d1d35bb3e50/41698_2024_724_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab94/11550450/943314219070/41698_2024_724_Fig9_HTML.jpg

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Identification of cuproptosis hub genes contributing to the immune microenvironment in ulcerative colitis using bioinformatic analysis and experimental verification.利用生物信息学分析和实验验证鉴定溃疡性结肠炎中与免疫微环境相关的铜死亡枢纽基因。
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