A potassium-chloride co-transporter with altered genome architecture functions as a suppressor in glioma.
Hongwei LiuZhouyang PanXuelei LinLong ChenQi YangWei ZhangLuohuan DaiYihao ZhangWang LiYinhua ChenKang PengSiyi WanggouFeiyue ZengXue-Jun LiPublished in: Journal of cellular and molecular medicine (2024)
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 A 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.
Keyphrases
- poor prognosis
- single cell
- gene expression
- long non coding rna
- genome wide
- cell therapy
- resting state
- dna methylation
- transcription factor
- cell proliferation
- high grade
- white matter
- functional connectivity
- wastewater treatment
- electronic health record
- multiple sclerosis
- binding protein
- big data
- adverse drug
- brain injury
- mesenchymal stem cells
- deep learning
- heat shock
- cerebral ischemia
- heat shock protein
- heat stress