有氧糖酵解是恶性肿瘤赖以生存的重要代谢途径，肿瘤微环境是如何影响膀胱癌能量代谢的机制尚不清楚。我们前期研究发现，膀胱癌细胞中有氧糖酵解限速酶LDH-A高表达，且和肿瘤进展相关；LDH-A表达上调的机制可能是肿瘤相关成纤维细胞（CAFs）通过外泌体转运非编码RNA GATBCA1。本课题拟进一步通过共培养模型、RNA pull-down、蛋白泛素化检测、细胞外酸化率检测等方法，证实CAFs通过外泌体转运GATBCA1在增强膀胱癌细胞有氧糖酵解中的关键作用；阐明GATBCA1调控LDH-A启动子转录活性的分子机制。本项目紧紧围绕“CAFs通过外泌体转运GATBCA1，通过HSP90/c-Myc轴上调LDH-A表达增强膀胱癌细胞有氧糖酵解”这一科学假说，从GATBCA1的全新调控机制入手，揭示其促进膀胱癌有氧糖酵解的具体机制，为开发膀胱癌治疗新靶点提供原创性的科学依据。

Aerobic glycolysis is an important metabolic pathway for malignant tumors to survive, the mechanism of how tumor microenvironment affects the energy metabolism of bladder cancer is unclear. Our previous research found that the aerobic glycolytic rate-limiting enzyme LDH-A is highly expressed in bladder cancer cells and is related to tumor progression; the mechanism of upregulation of LDH-A expression may be that tumor-associated fibroblasts (CAFs) pass through exosome loaded with non-coding RNA GATBCA1. This project intends to further confirm the key role of CAFs in the transport of GATBCA1 through exosomes in enhancing aerobic glycolysis of bladder cancer cells through co-culture models, RNA pull-down, protein ubiquitination detection, and extracellular acidification rate detection; to clarify the molecular mechanism of GATBCA1 regulating the transcriptional activity of LDH-A promoter. This project focuses on the scientific hypothesis that CAFs transport GATBCA1 through exosomes and upregulate LDH-A expression through the HSP90/c-Myc axis to enhance aerobic glycolysis of bladder cancer cells. Its specific mechanism for promoting bladder cancer aerobic glycolysis provides an original scientific basis for the development of new therapeutic targets for bladder cancer.