Single-Cell Sequencing Reveals that DBI is the Key Gene and Potential Therapeutic Target in Quiescent Bladder Cancer Stem Cells
Background: Drug resistance and recurrence often develop during the treatment of muscle-invasive bladder cancer (MIBC). The existence of cancer stem cells (CSCs) in MIBC makes the formulation of effective treatment strategies extremely challenging. We aimed to use single-cell RNA sequencing approach...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.904536/full |
| _version_ | 1818544801161674752 |
|---|---|
| author | Jiaxi Yao Jiaxi Yao Yue Liu Jitao Yang Jitao Yang Mengling Li Simin Li Bo Zhang Rui Yang Yuchong Zhang Xiaoyu Cui Xiaoyu Cui ChunQing Feng |
| author_facet | Jiaxi Yao Jiaxi Yao Yue Liu Jitao Yang Jitao Yang Mengling Li Simin Li Bo Zhang Rui Yang Yuchong Zhang Xiaoyu Cui Xiaoyu Cui ChunQing Feng |
| author_sort | Jiaxi Yao |
| collection | DOAJ |
| description | Background: Drug resistance and recurrence often develop during the treatment of muscle-invasive bladder cancer (MIBC). The existence of cancer stem cells (CSCs) in MIBC makes the formulation of effective treatment strategies extremely challenging. We aimed to use single-cell RNA sequencing approaches to identify CSCs and evaluate their molecular characteristics and to discover possible therapeutic measures.Methods: GEO data sets GSE130001 and GSE146137 were used to construct an expression matrix. After cells were identified by type, malignant epithelial cells inferred by InferCNV were extracted for stemness evaluation. The subset of cells with the highest stemness was subjected to weighted gene coexpression network analysis (WGCNA) and pseudotime analysis to identify key genes. In addition, we predicted drug sensitivity relationships for key genes in CTD and predicted the correlation between drugs and survival through siGDC.Results: We found that there were some CSCs in MIBC samples. The CSC population was heterogeneous during tumor development and was divided into quiescent and proliferating CSCs. We identified DBI as the key gene in quiescent CSCs. Analysis of a TCGA data set showed that higher DBI expression indicated higher histological grade. In addition, we predicted that acetaminophen can reduce DBI expression, thereby reducing the stemness of CSCs. Thus, we identified a potential new use of acetaminophen.Conclusion: We systematically explored CSCs in tumors and determined that DBI may be a key gene and potential therapeutic target in quiescent CSCs. In addition, we confirmed that acetaminophen may be a candidate drug targeting CSCs, improving our understanding of CSC-targeting therapeutic strategies. |
| first_indexed | 2024-12-11T22:53:12Z |
| format | Article |
| id | doaj.art-763392ee3ee64bef882cc1e1a446fed7 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-11T22:53:12Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-763392ee3ee64bef882cc1e1a446fed72022-12-22T00:47:21ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-06-011310.3389/fgene.2022.904536904536Single-Cell Sequencing Reveals that DBI is the Key Gene and Potential Therapeutic Target in Quiescent Bladder Cancer Stem CellsJiaxi Yao0Jiaxi Yao1Yue Liu2Jitao Yang3Jitao Yang4Mengling Li5Simin Li6Bo Zhang7Rui Yang8Yuchong Zhang9Xiaoyu Cui10Xiaoyu Cui11ChunQing Feng12Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, ChinaDepartment of Urology, The First Affiliated Hospital of China Medical University, Shenyang, ChinaDepartment of Urology, The First Affiliated Hospital of China Medical University, Shenyang, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, ChinaDepartment of Clinical Epidemiology and Center of Evidence-Based Medicine, The First Affiliated Hospital of China Medical University, Shenyang, ChinaDepartment of Clinical Epidemiology and Center of Evidence-Based Medicine, The First Affiliated Hospital of China Medical University, Shenyang, ChinaDepartment of Clinical Epidemiology and Center of Evidence-Based Medicine, The First Affiliated Hospital of China Medical University, Shenyang, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, ChinaCollege of Medicine and Biological Information Engineering, Northeastern University, Shenyang, ChinaKey Laboratory of Data Analytics and Optimization for Smart Industry, Northeastern University, Shenyang, ChinaDepartment of Urology Surgery, The Central Hospital Affiliated to Shenyang Medical College, Shenyang, ChinaBackground: Drug resistance and recurrence often develop during the treatment of muscle-invasive bladder cancer (MIBC). The existence of cancer stem cells (CSCs) in MIBC makes the formulation of effective treatment strategies extremely challenging. We aimed to use single-cell RNA sequencing approaches to identify CSCs and evaluate their molecular characteristics and to discover possible therapeutic measures.Methods: GEO data sets GSE130001 and GSE146137 were used to construct an expression matrix. After cells were identified by type, malignant epithelial cells inferred by InferCNV were extracted for stemness evaluation. The subset of cells with the highest stemness was subjected to weighted gene coexpression network analysis (WGCNA) and pseudotime analysis to identify key genes. In addition, we predicted drug sensitivity relationships for key genes in CTD and predicted the correlation between drugs and survival through siGDC.Results: We found that there were some CSCs in MIBC samples. The CSC population was heterogeneous during tumor development and was divided into quiescent and proliferating CSCs. We identified DBI as the key gene in quiescent CSCs. Analysis of a TCGA data set showed that higher DBI expression indicated higher histological grade. In addition, we predicted that acetaminophen can reduce DBI expression, thereby reducing the stemness of CSCs. Thus, we identified a potential new use of acetaminophen.Conclusion: We systematically explored CSCs in tumors and determined that DBI may be a key gene and potential therapeutic target in quiescent CSCs. In addition, we confirmed that acetaminophen may be a candidate drug targeting CSCs, improving our understanding of CSC-targeting therapeutic strategies.https://www.frontiersin.org/articles/10.3389/fgene.2022.904536/fullcancer stem cellsbladder cancerscRNA-seqacetaminophenDBI |
| spellingShingle | Jiaxi Yao Jiaxi Yao Yue Liu Jitao Yang Jitao Yang Mengling Li Simin Li Bo Zhang Rui Yang Yuchong Zhang Xiaoyu Cui Xiaoyu Cui ChunQing Feng Single-Cell Sequencing Reveals that DBI is the Key Gene and Potential Therapeutic Target in Quiescent Bladder Cancer Stem Cells Frontiers in Genetics cancer stem cells bladder cancer scRNA-seq acetaminophen DBI |
| title | Single-Cell Sequencing Reveals that DBI is the Key Gene and Potential Therapeutic Target in Quiescent Bladder Cancer Stem Cells |
| title_full | Single-Cell Sequencing Reveals that DBI is the Key Gene and Potential Therapeutic Target in Quiescent Bladder Cancer Stem Cells |
| title_fullStr | Single-Cell Sequencing Reveals that DBI is the Key Gene and Potential Therapeutic Target in Quiescent Bladder Cancer Stem Cells |
| title_full_unstemmed | Single-Cell Sequencing Reveals that DBI is the Key Gene and Potential Therapeutic Target in Quiescent Bladder Cancer Stem Cells |
| title_short | Single-Cell Sequencing Reveals that DBI is the Key Gene and Potential Therapeutic Target in Quiescent Bladder Cancer Stem Cells |
| title_sort | single cell sequencing reveals that dbi is the key gene and potential therapeutic target in quiescent bladder cancer stem cells |
| topic | cancer stem cells bladder cancer scRNA-seq acetaminophen DBI |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.904536/full |
| work_keys_str_mv | AT jiaxiyao singlecellsequencingrevealsthatdbiisthekeygeneandpotentialtherapeutictargetinquiescentbladdercancerstemcells AT jiaxiyao singlecellsequencingrevealsthatdbiisthekeygeneandpotentialtherapeutictargetinquiescentbladdercancerstemcells AT yueliu singlecellsequencingrevealsthatdbiisthekeygeneandpotentialtherapeutictargetinquiescentbladdercancerstemcells AT jitaoyang singlecellsequencingrevealsthatdbiisthekeygeneandpotentialtherapeutictargetinquiescentbladdercancerstemcells AT jitaoyang singlecellsequencingrevealsthatdbiisthekeygeneandpotentialtherapeutictargetinquiescentbladdercancerstemcells AT menglingli singlecellsequencingrevealsthatdbiisthekeygeneandpotentialtherapeutictargetinquiescentbladdercancerstemcells AT siminli singlecellsequencingrevealsthatdbiisthekeygeneandpotentialtherapeutictargetinquiescentbladdercancerstemcells AT bozhang singlecellsequencingrevealsthatdbiisthekeygeneandpotentialtherapeutictargetinquiescentbladdercancerstemcells AT ruiyang singlecellsequencingrevealsthatdbiisthekeygeneandpotentialtherapeutictargetinquiescentbladdercancerstemcells AT yuchongzhang singlecellsequencingrevealsthatdbiisthekeygeneandpotentialtherapeutictargetinquiescentbladdercancerstemcells AT xiaoyucui singlecellsequencingrevealsthatdbiisthekeygeneandpotentialtherapeutictargetinquiescentbladdercancerstemcells AT xiaoyucui singlecellsequencingrevealsthatdbiisthekeygeneandpotentialtherapeutictargetinquiescentbladdercancerstemcells AT chunqingfeng singlecellsequencingrevealsthatdbiisthekeygeneandpotentialtherapeutictargetinquiescentbladdercancerstemcells |