Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China.
J Cell Mol Med. 2024 May;28(9):e18352. doi: 10.1111/jcmm.18352.
Gliomas, the most lethal tumours in brain, have a poor prognosis despite accepting standard treatment. Limited benefits from current therapies can be attributed to genetic, epigenetic and microenvironmental cues that affect cell programming and drive tumour heterogeneity. Through the analysis of Hi-C data, we identified a potassium-chloride co-transporter SLC12A5 associated with disrupted topologically associating domain which was downregulated in tumour tissues. Multiple independent glioma cohorts were included to analyse the characterization of SLC12A5 and found it was significantly associated with pathological features, prognostic value, genomic alterations, transcriptional landscape and drug response. We constructed two SLC12A5 overexpression cell lines to verify the function of SLC12A5 that suppressed tumour cell proliferation and migration in vitro. In addition, SLC12A5 was also positively associated with GABA receptor activity and negatively associated with pro-tumour immune signatures and immunotherapy response. Collectively, our study provides a comprehensive characterization of SLC12A5 in glioma and supports SLC12A5 as a potential suppressor of disease progression.
脑胶质瘤是最致命的脑部肿瘤，尽管接受了标准治疗，预后仍很差。目前的治疗方法收效甚微，这可以归因于遗传、表观遗传和微环境线索，这些线索影响细胞编程并驱动肿瘤异质性。通过对 Hi-C 数据的分析，我们鉴定出一种与拓扑关联域破坏相关的钾氯共转运蛋白 SLC12A5，其在肿瘤组织中下调。纳入多个独立的脑胶质瘤队列来分析 SLC12A5 的特征，发现它与病理特征、预后价值、基因组改变、转录图谱和药物反应显著相关。我们构建了两个 SLC12A5 过表达细胞系来验证 SLC12A5 的功能，发现其在体外抑制肿瘤细胞增殖和迁移。此外，SLC12A5 还与 GABA 受体活性呈正相关，与促肿瘤免疫特征和免疫治疗反应呈负相关。总之，我们的研究全面描述了 SLC12A5 在脑胶质瘤中的作用，并支持 SLC12A5 作为疾病进展的潜在抑制剂。
