Unveiling cell-type-specific microRNA networks through alternative polyadenylation in glioblastoma
Abstract Background Glioblastoma multiforme (GBM) is characterized by its cellular complexity, with a microenvironment consisting of diverse cell types, including oligodendrocyte precursor cells (OPCs) and neoplastic CD133 + radial glia-like cells. This study focuses on exploring the distinct cellul...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | BMC Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12915-024-02104-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585352858042368 |
|---|---|
| author | Mert Cihan Greta Schmauck Maximilian Sprang Miguel A. Andrade-Navarro |
| author_facet | Mert Cihan Greta Schmauck Maximilian Sprang Miguel A. Andrade-Navarro |
| author_sort | Mert Cihan |
| collection | DOAJ |
| description | Abstract Background Glioblastoma multiforme (GBM) is characterized by its cellular complexity, with a microenvironment consisting of diverse cell types, including oligodendrocyte precursor cells (OPCs) and neoplastic CD133 + radial glia-like cells. This study focuses on exploring the distinct cellular transitions in GBM, emphasizing the role of alternative polyadenylation (APA) in modulating microRNA-binding and post-transcriptional regulation. Results Our research identified unique APA profiles that signify the transitional phases between neoplastic cells and OPCs, underscoring the importance of APA in cellular identity and transformation in GBM. A significant finding was the disconnection between differential APA events and gene expression alterations, indicating that APA operates as an independent regulatory mechanism. We also highlighted the specific genes in neoplastic cells and OPCs that lose microRNA-binding sites due to APA, which are crucial for maintaining stem cell characteristics and DNA repair, respectively. The constructed networks of microRNA-transcription factor-target genes provide insights into the cellular mechanisms influencing cancer cell survival and therapeutic resistance. Conclusions This study elucidates the APA-driven regulatory framework within GBM, spotlighting its influence on cell state transitions and microRNA network dynamics. Our comprehensive analysis using single-cell RNA sequencing data to investigate the microRNA-binding sites altered by APA profiles offers a robust foundation for future research, presenting a novel approach to understanding and potentially targeting the complex molecular interplay in GBM. |
| format | Article |
| id | doaj-art-58c9f8f00d6e41aaa135a94a143a351a |
| institution | Kabale University |
| issn | 1741-7007 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj-art-58c9f8f00d6e41aaa135a94a143a351a2025-01-26T12:52:36ZengBMCBMC Biology1741-70072025-01-0123111610.1186/s12915-024-02104-8Unveiling cell-type-specific microRNA networks through alternative polyadenylation in glioblastomaMert Cihan0Greta Schmauck1Maximilian Sprang2Miguel A. Andrade-Navarro3Faculty of Biology, Johannes Gutenberg University MainzFaculty of Biology, Johannes Gutenberg University MainzFaculty of Biology, Johannes Gutenberg University MainzFaculty of Biology, Johannes Gutenberg University MainzAbstract Background Glioblastoma multiforme (GBM) is characterized by its cellular complexity, with a microenvironment consisting of diverse cell types, including oligodendrocyte precursor cells (OPCs) and neoplastic CD133 + radial glia-like cells. This study focuses on exploring the distinct cellular transitions in GBM, emphasizing the role of alternative polyadenylation (APA) in modulating microRNA-binding and post-transcriptional regulation. Results Our research identified unique APA profiles that signify the transitional phases between neoplastic cells and OPCs, underscoring the importance of APA in cellular identity and transformation in GBM. A significant finding was the disconnection between differential APA events and gene expression alterations, indicating that APA operates as an independent regulatory mechanism. We also highlighted the specific genes in neoplastic cells and OPCs that lose microRNA-binding sites due to APA, which are crucial for maintaining stem cell characteristics and DNA repair, respectively. The constructed networks of microRNA-transcription factor-target genes provide insights into the cellular mechanisms influencing cancer cell survival and therapeutic resistance. Conclusions This study elucidates the APA-driven regulatory framework within GBM, spotlighting its influence on cell state transitions and microRNA network dynamics. Our comprehensive analysis using single-cell RNA sequencing data to investigate the microRNA-binding sites altered by APA profiles offers a robust foundation for future research, presenting a novel approach to understanding and potentially targeting the complex molecular interplay in GBM.https://doi.org/10.1186/s12915-024-02104-8GlioblastomaMicroRNAAlternative polyadenylationStem cellSingle-cell RNA |
| spellingShingle | Mert Cihan Greta Schmauck Maximilian Sprang Miguel A. Andrade-Navarro Unveiling cell-type-specific microRNA networks through alternative polyadenylation in glioblastoma BMC Biology Glioblastoma MicroRNA Alternative polyadenylation Stem cell Single-cell RNA |
| title | Unveiling cell-type-specific microRNA networks through alternative polyadenylation in glioblastoma |
| title_full | Unveiling cell-type-specific microRNA networks through alternative polyadenylation in glioblastoma |
| title_fullStr | Unveiling cell-type-specific microRNA networks through alternative polyadenylation in glioblastoma |
| title_full_unstemmed | Unveiling cell-type-specific microRNA networks through alternative polyadenylation in glioblastoma |
| title_short | Unveiling cell-type-specific microRNA networks through alternative polyadenylation in glioblastoma |
| title_sort | unveiling cell type specific microrna networks through alternative polyadenylation in glioblastoma |
| topic | Glioblastoma MicroRNA Alternative polyadenylation Stem cell Single-cell RNA |
| url | https://doi.org/10.1186/s12915-024-02104-8 |
| work_keys_str_mv | AT mertcihan unveilingcelltypespecificmicrornanetworksthroughalternativepolyadenylationinglioblastoma AT gretaschmauck unveilingcelltypespecificmicrornanetworksthroughalternativepolyadenylationinglioblastoma AT maximiliansprang unveilingcelltypespecificmicrornanetworksthroughalternativepolyadenylationinglioblastoma AT miguelaandradenavarro unveilingcelltypespecificmicrornanetworksthroughalternativepolyadenylationinglioblastoma |