Integration of multi-omics data revealed the orphan CpG islands and enhancer-dominated cis-regulatory network in glioma
The complex transcriptional regulatory network leads to the poor prognosis of glioma. The role of orphan CpG islands (oCGIs) in the transcriptional regulatory network has been overlooked. We conducted a comprehensive exploration of the <i>cis</i>-regulatory roles of oCGIs and enhancers by integrating multi-omics data. Direct regulation of target genes by oCGIs or enhancers is of great importance in the <i>cis</i>-regulatory network. Furthermore, based on single-cell multi-omics data, we found that the highly activated <i>cis</i>-regulatory network in cluster 2 (C2) sustains the high proliferative potential of glioma cells. The upregulation of oCGIs and enhancers related genes in C2 results in glioma patients exhibiting resistance to radiotherapy and chemotherapy. These findings were further validated through glioma cell line related experiments. Our study offers insight into the pathogenesis of glioma and provides a strategy to treat this challenging disease.
Authors
- Penglei Yao
- Junming Jia
- Xinqi Ma
- Shuqing Gu (ORCID: https://orcid.org/0000-0002-6768-5644)
- Qingsong Yang (ORCID: https://orcid.org/0000-0003-2904-1503)
- Ke He (ORCID: https://orcid.org/0000-0002-9194-8408)
- Zeren Chen
- Weihua Li (ORCID: https://orcid.org/0009-0006-2163-3335)
- Yang Li (ORCID: https://orcid.org/0000-0003-4022-7341)
- Jiawei Yao (ORCID: https://orcid.org/0009-0009-1090-922X)
- Yan Zhao (ORCID: https://orcid.org/0009-0000-3608-3715)
- Guangzhi Wang (ORCID: https://orcid.org/0000-0002-0838-4366)
- Mian Guo (ORCID: https://orcid.org/0000-0002-1475-1935)
- Shan Yu (ORCID: https://orcid.org/0009-0000-5650-4505)
- Kunliang Chen
Institutions
- Qiqihar University (CN)
- Harbin Medical University (CN)
- Second Affiliated Hospital of Harbin Medical University (CN)
- Qiqihar Institute of Engineering (CN)
- Qiqihar Medical University (CN)
Publication Details
- Journal
- iScience
- Published
- 2024-09-13
- DOI
- https://doi.org/10.1016/j.isci.2024.110946
- Citations
- 1
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.23
Funders
- Key Research and Development Program of Heilongjiang
- National Natural Science Foundation of China
- Science, Technology and Innovation Commission of Shenzhen Municipality
- Shenzhen Science and Technology Innovation Program