Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer
Background: Ulcerative colitis (UC) is a well-known risk factor for developing colitis-associated colorectal cancer (CAC). However, the molecular mechanism of the pathogenesis of CAC remains unclear. This study aimed to explore candidate genes involved in the tumorigenesis of CAC.Methods: GSE75214 a...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.945414/full |
| _version_ | 1811314621503504384 |
|---|---|
| author | Can Lu Can Lu Xiaopeng Zhang Xiaopeng Zhang Yang Luo Jingang Huang Jingang Huang Minhao Yu |
| author_facet | Can Lu Can Lu Xiaopeng Zhang Xiaopeng Zhang Yang Luo Jingang Huang Jingang Huang Minhao Yu |
| author_sort | Can Lu |
| collection | DOAJ |
| description | Background: Ulcerative colitis (UC) is a well-known risk factor for developing colitis-associated colorectal cancer (CAC). However, the molecular mechanism of the pathogenesis of CAC remains unclear. This study aimed to explore candidate genes involved in the tumorigenesis of CAC.Methods: GSE75214 and the Cancer Genome Atlas Program (TCGA) dataset were used to analyze the differentially expressed genes (DEGs) in UC and colorectal cancer (CRC), respectively. Survival-hub genes were identified from these DEGs by sequentially constructing a protein–protein interaction network, selecting hub genes, and conducting survival analysis. Regulatory signatures were also predicted on these genes through the online database. Apcmin/+ and UC mice models were used to validate the expression of the above-predicted molecules. Gene set enrichment analysis and CIBERSORT were performed to explore the enriched molecular pathways and associated tissue-infiltrating immune cells of genes.Results: Here, 376 common DEGs were identified from the GSE75214 and TCGA datasets. Through survival-hub gene selection and in vivo experiments, we confirmed that CXCL10 and CXCL11 were significantly upregulated in UC and CRC. We also proved that miR-34a-5p and miR-203a-5p were potential regulators of CXCL10 and CXCL11. Meanwhile, CXCL10 and CXCL11 may activate the JAK–STAT signaling pathway via the interaction with cytokine receptors in UC. Furthermore, CXCL10 and CXCL11 were positively associated with the tissue infiltration of proinflammatory M1 macrophages in UC and CRC.Conclusion: CXCL10 and CXCL11 may act as the candidate genes involved in the tumorigenesis of CAC and potential therapeutic targets to prevent the development of CAC from UC. |
| first_indexed | 2024-04-13T11:14:30Z |
| format | Article |
| id | doaj.art-93f19ca093d7442c9bb346a7ed0927a7 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T11:14:30Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-93f19ca093d7442c9bb346a7ed0927a72022-12-22T02:49:01ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.945414945414Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancerCan Lu0Can Lu1Xiaopeng Zhang2Xiaopeng Zhang3Yang Luo4Jingang Huang5Jingang Huang6Minhao Yu7Faculty of Medicine, Ludwig-Maximilians University, Munich, GermanyDepartment of Colorectal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaSchool of Medicine, Technical University of Munich, Munich, GermanyGastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaMedical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaBackground: Ulcerative colitis (UC) is a well-known risk factor for developing colitis-associated colorectal cancer (CAC). However, the molecular mechanism of the pathogenesis of CAC remains unclear. This study aimed to explore candidate genes involved in the tumorigenesis of CAC.Methods: GSE75214 and the Cancer Genome Atlas Program (TCGA) dataset were used to analyze the differentially expressed genes (DEGs) in UC and colorectal cancer (CRC), respectively. Survival-hub genes were identified from these DEGs by sequentially constructing a protein–protein interaction network, selecting hub genes, and conducting survival analysis. Regulatory signatures were also predicted on these genes through the online database. Apcmin/+ and UC mice models were used to validate the expression of the above-predicted molecules. Gene set enrichment analysis and CIBERSORT were performed to explore the enriched molecular pathways and associated tissue-infiltrating immune cells of genes.Results: Here, 376 common DEGs were identified from the GSE75214 and TCGA datasets. Through survival-hub gene selection and in vivo experiments, we confirmed that CXCL10 and CXCL11 were significantly upregulated in UC and CRC. We also proved that miR-34a-5p and miR-203a-5p were potential regulators of CXCL10 and CXCL11. Meanwhile, CXCL10 and CXCL11 may activate the JAK–STAT signaling pathway via the interaction with cytokine receptors in UC. Furthermore, CXCL10 and CXCL11 were positively associated with the tissue infiltration of proinflammatory M1 macrophages in UC and CRC.Conclusion: CXCL10 and CXCL11 may act as the candidate genes involved in the tumorigenesis of CAC and potential therapeutic targets to prevent the development of CAC from UC.https://www.frontiersin.org/articles/10.3389/fgene.2022.945414/fullulcerative colitiscolorectal cancercolitis-associated colorectal cancerdifferentially expressed genesTCGA |
| spellingShingle | Can Lu Can Lu Xiaopeng Zhang Xiaopeng Zhang Yang Luo Jingang Huang Jingang Huang Minhao Yu Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer Frontiers in Genetics ulcerative colitis colorectal cancer colitis-associated colorectal cancer differentially expressed genes TCGA |
| title | Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer |
| title_full | Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer |
| title_fullStr | Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer |
| title_full_unstemmed | Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer |
| title_short | Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer |
| title_sort | identification of cxcl10 and cxcl11 as the candidate genes involving the development of colitis associated colorectal cancer |
| topic | ulcerative colitis colorectal cancer colitis-associated colorectal cancer differentially expressed genes TCGA |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.945414/full |
| work_keys_str_mv | AT canlu identificationofcxcl10andcxcl11asthecandidategenesinvolvingthedevelopmentofcolitisassociatedcolorectalcancer AT canlu identificationofcxcl10andcxcl11asthecandidategenesinvolvingthedevelopmentofcolitisassociatedcolorectalcancer AT xiaopengzhang identificationofcxcl10andcxcl11asthecandidategenesinvolvingthedevelopmentofcolitisassociatedcolorectalcancer AT xiaopengzhang identificationofcxcl10andcxcl11asthecandidategenesinvolvingthedevelopmentofcolitisassociatedcolorectalcancer AT yangluo identificationofcxcl10andcxcl11asthecandidategenesinvolvingthedevelopmentofcolitisassociatedcolorectalcancer AT jinganghuang identificationofcxcl10andcxcl11asthecandidategenesinvolvingthedevelopmentofcolitisassociatedcolorectalcancer AT jinganghuang identificationofcxcl10andcxcl11asthecandidategenesinvolvingthedevelopmentofcolitisassociatedcolorectalcancer AT minhaoyu identificationofcxcl10andcxcl11asthecandidategenesinvolvingthedevelopmentofcolitisassociatedcolorectalcancer |