m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer
BACKGROUND: Gene expression can be posttranscriptionally regulated by a complex network of proteins. N1-methyladenosine (m1A) is a newly validated RNA modification. However, little is known about both its influence and biogenesis in tumor development. METHODS: This study analyzed TCGA data of patien...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-10-01
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| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523319301925 |
| _version_ | 1819076320787693568 |
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| author | Yueshui Zhao Qijie Zhao Parham Jabbarzadeh Kaboli Jing Shen Mingxing Li Xu Wu Jianhua Yin Hanyu Zhang Yuanlin Wu Ling Lin Lingling Zhang Lin Wan Qinglian Wen Xiang Li Chi Hin Cho Tao Yi Jing Li Zhangang Xiao |
| author_facet | Yueshui Zhao Qijie Zhao Parham Jabbarzadeh Kaboli Jing Shen Mingxing Li Xu Wu Jianhua Yin Hanyu Zhang Yuanlin Wu Ling Lin Lingling Zhang Lin Wan Qinglian Wen Xiang Li Chi Hin Cho Tao Yi Jing Li Zhangang Xiao |
| author_sort | Yueshui Zhao |
| collection | DOAJ |
| description | BACKGROUND: Gene expression can be posttranscriptionally regulated by a complex network of proteins. N1-methyladenosine (m1A) is a newly validated RNA modification. However, little is known about both its influence and biogenesis in tumor development. METHODS: This study analyzed TCGA data of patients with five kinds of gastrointestinal (GI) cancers. Using data from cBioPortal, molecular features of the nine known m1A-related enzymes in GI cancers were investigated. Using a variety of bioinformatics approach, the impact of m1A regulators on its downstream signaling pathway was studied. To further confirm this regulation, the effect of m1A writer ALKBH3 knockdown was studied using RNA-seq data from published database. RESULTS: Dysregulation and multiple types of genetic alteration of putative m1A-related enzymes in tumor samples were observed. The ErbB and mTOR pathways with ErbB2, mTOR, and AKT1S1 hub genes were identified as being regulated by m1A-related enzymes. The expression of both ErbB2 and AKT1S1 was decreased after m1A writer ALKBH3 knockdown. Furthermore, Gene Ontology analysis revealed that m1A downstream genes were associated with cell proliferation, and the results showed that m1A genes are reliably linked to mTOR. CONCLUSION: This study demonstrated for the first time the dysregulation of m1A regulators in GI cancer and its signaling pathways and will contribute to the understanding of RNA modification in cancer. |
| first_indexed | 2024-12-21T18:39:26Z |
| format | Article |
| id | doaj.art-0c5c187891e34b1eb600e174cdcabe21 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-21T18:39:26Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-0c5c187891e34b1eb600e174cdcabe212022-12-21T18:54:03ZengElsevierTranslational Oncology1936-52332019-10-01121013231333m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal CancerYueshui Zhao0Qijie Zhao1Parham Jabbarzadeh Kaboli2Jing Shen3Mingxing Li4Xu Wu5Jianhua Yin6Hanyu Zhang7Yuanlin Wu8Ling Lin9Lingling Zhang10Lin Wan11Qinglian Wen12Xiang Li13Chi Hin Cho14Tao Yi15Jing Li16Zhangang Xiao17Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR ChinaDepartment of Hematology and Oncology, The Children’s Hospital of Soochow, Jiangsu, ChinaDepartment of Oncology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, PR ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR ChinaSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaDepartment of Oncology and Hematology, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, Sichuan, China; Address all correspondence to: Jing Li, Department of Oncology and Hematology, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, Sichuan, China. or Zhangang Xiao, Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China.Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China; South Sichuan Institution for Translational Medicine, Luzhou, 646000, Sichuan, PR China; Address all correspondence to: Jing Li, Department of Oncology and Hematology, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, Sichuan, China. or Zhangang Xiao, Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China.BACKGROUND: Gene expression can be posttranscriptionally regulated by a complex network of proteins. N1-methyladenosine (m1A) is a newly validated RNA modification. However, little is known about both its influence and biogenesis in tumor development. METHODS: This study analyzed TCGA data of patients with five kinds of gastrointestinal (GI) cancers. Using data from cBioPortal, molecular features of the nine known m1A-related enzymes in GI cancers were investigated. Using a variety of bioinformatics approach, the impact of m1A regulators on its downstream signaling pathway was studied. To further confirm this regulation, the effect of m1A writer ALKBH3 knockdown was studied using RNA-seq data from published database. RESULTS: Dysregulation and multiple types of genetic alteration of putative m1A-related enzymes in tumor samples were observed. The ErbB and mTOR pathways with ErbB2, mTOR, and AKT1S1 hub genes were identified as being regulated by m1A-related enzymes. The expression of both ErbB2 and AKT1S1 was decreased after m1A writer ALKBH3 knockdown. Furthermore, Gene Ontology analysis revealed that m1A downstream genes were associated with cell proliferation, and the results showed that m1A genes are reliably linked to mTOR. CONCLUSION: This study demonstrated for the first time the dysregulation of m1A regulators in GI cancer and its signaling pathways and will contribute to the understanding of RNA modification in cancer.http://www.sciencedirect.com/science/article/pii/S1936523319301925 |
| spellingShingle | Yueshui Zhao Qijie Zhao Parham Jabbarzadeh Kaboli Jing Shen Mingxing Li Xu Wu Jianhua Yin Hanyu Zhang Yuanlin Wu Ling Lin Lingling Zhang Lin Wan Qinglian Wen Xiang Li Chi Hin Cho Tao Yi Jing Li Zhangang Xiao m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer Translational Oncology |
| title | m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer |
| title_full | m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer |
| title_fullStr | m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer |
| title_full_unstemmed | m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer |
| title_short | m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer |
| title_sort | m1a regulated genes modulate pi3k akt mtor and erbb pathways in gastrointestinal cancer |
| url | http://www.sciencedirect.com/science/article/pii/S1936523319301925 |
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