ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1604758
This article is part of the Research TopicCancer Immunity and Metabolic Reprogramming: Pioneering Precision ImmunotherapiesView all articles
Identification of Lactylation-Associated Immune and Metabolic Regulators in Bladder Cancer via Integrated Bulk and Single-Cell Transcriptomics
Provisionally accepted
- 1Sun Yat-sen Memorial Hospital, Guangzhou, China
- 2The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
BackgroundLactate-driven metabolic reprogramming and histone lactylation play pivotal roles in bladder cancer (BLCA) progression, yet their underlying mechanisms and regulatory genes remain poorly understood.MethodsUsing transcriptomic data from The Cancer Genome Atlas (TCGA), we identified lactylation-associated genes and constructed a prognostic signature. Comprehensive bioinformatics analyses were conducted to assess immune infiltration, tumor microenvironment characteristics, and the lactylation landscape at the single-cell level. Furthermore, we performed in vitro experiments to evaluate the biological functions of key lactylation-related genes in BLCA cells.ResultsSix lactylation-related hub genes were identified, among which FASN and RUNX2 were significantly upregulated in BLCA and associated with poor prognosis. Single-cell analyses revealed elevated lactylation signatures in tumor epithelial and immune cells. Knockdown of FASN or RUNX2 in BLCA cell lines significantly suppressed cell proliferation, induced apoptosis, and reduced intracellular lactate levels. Correspondingly, global protein lactylation was diminished, with dominant modification signals observed around 40 kDa, indicating a potential set of non-histone proteins as key functional targets. ConclusionsOur study highlights a metabolic-enzymatic axis wherein FASN and RUNX2 regulate lactate-driven protein lactylation in BLCA. These findings provide new insights into the non-histone functions of lactylation and suggest potential therapeutic targets at the intersection of metabolism and tumor immunity.
Keywords: lactylation, immunological regulators, Bladder cancer, single cell, metabolic regulators
Received: 02 Apr 2025; Accepted: 23 Jun 2025.
Copyright: © 2025 Chen, Sun and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaoyan Liu, Sun Yat-sen Memorial Hospital, Guangzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.