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2-羟基异丁酰化的蛋白质组和翻译后修饰分析揭示口腔腺样囊性癌中的糖酵解途径。

Analysis of proteome and post-translational modifications of 2-hydroxyisobutyrylation reveals the glycolysis pathway in oral adenoid cystic carcinoma.

机构信息

Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Jinan University, Shenzhen, 518020, Guangdong, China.

Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, China.

出版信息

World J Surg Oncol. 2023 Sep 23;21(1):301. doi: 10.1186/s12957-023-03155-x.

DOI:10.1186/s12957-023-03155-x
PMID:37741973
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10517466/
Abstract

PURPOSE

Oral adenoid cystic carcinoma (OACC) has high rates of both local-regional recurrence and distant metastasis. The objective of this study is to investigate the impact of Khib on OACC and its potential as a targeted therapeutic intervention. EXPERIMENTAL DESIGN: We investigated the DEPs (differentially expressed proteins) and DHMPs between OACC-T and OACC-N using LC-MS/MS-based quantitative proteomics and using several bioinformatics methods, including GO enrichment analysis, KEGG pathway analysis, subcellular localization prediction, MEA (motif enrichment analysis), and PPI (protein-protein interaction networks) to illustrate how Khib modification interfere with OACC evolution.

RESULTS

Compared OACC-tumor samples (OACC-T) with the adjacent normal samples (OACC-N), there were 3243 of the DEPs and 2011 Khib sites were identified on 764 proteins (DHMPs). DEPs and DHMPs were strongly associated to glycolysis pathway. GAPDH of K254, ENO of K228, and PGK1 of K323 were modified by Khib in OACC-T. Khib may increase the catalytic efficiency to promote glycolysis pathway and favor OACC progression.

CONCLUSIONS AND CLINICAL RELEVANCE

Khib may play a significant role in the mechanism of OACC progression by influencing the enzyme activity of the glycolysis pathway. These findings may provide new therapeutic options of OACC.

摘要

目的

口腔腺样囊性癌（OACC）具有较高的局部区域复发和远处转移率。本研究旨在探讨 Khib 对 OACC 的影响及其作为靶向治疗干预的潜力。

实验设计

我们使用基于 LC-MS/MS 的定量蛋白质组学技术研究了 OACC-T 和 OACC-N 之间的 DEPs（差异表达蛋白）和 DHMPs，并用几种生物信息学方法，包括 GO 富集分析、KEGG 通路分析、亚细胞定位预测、MEA（基序富集分析）和 PPI（蛋白质-蛋白质相互作用网络），说明了 Khib 修饰如何干扰 OACC 的进化。

结果

与相邻正常样本（OACC-N）相比，OACC 肿瘤样本（OACC-T）中鉴定出 3243 个 DEPs 和 764 个蛋白质上的 2011 个 Khib 位点（DHMPs）。DEPs 和 DHMPs 与糖酵解途径密切相关。Khib 在 OACC-T 中修饰了 K254 位的 GAPDH、K228 位的 ENO 和 K323 位的 PGK1。Khib 可能通过影响糖酵解途径的酶活性在 OACC 进展的机制中发挥重要作用。

结论和临床意义

Khib 可能通过影响糖酵解途径的酶活性在 OACC 进展的机制中发挥重要作用。这些发现可能为 OACC 提供新的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4af9/10517466/b6a5228d37e3/12957_2023_3155_Fig10_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4af9/10517466/bad5cebd6319/12957_2023_3155_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4af9/10517466/8be380fa6b64/12957_2023_3155_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4af9/10517466/45f14ebf0b16/12957_2023_3155_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4af9/10517466/f076caefd979/12957_2023_3155_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4af9/10517466/b6a5228d37e3/12957_2023_3155_Fig10_HTML.jpg

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