miR-26a attenuates colitis and colitis-associated cancer by targeting the multiple intestinal inflammatory pathways
Patients with inflammatory bowel disease are at increased risk for colitis-associated colorectal cancer (CAC). Therefore, controlling intestinal inflammation is a key therapeutic strategy for CAC. MicroRNAs (miRNAs or miRs) are a family of small noncoding RNAs that have the capacity to regulate fund...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253121000640 |
| _version_ | 1828144678621413376 |
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| author | Wei Zhang Xianghui Fu Jiansheng Xie Hongming Pan Weidong Han Wendong Huang |
| author_facet | Wei Zhang Xianghui Fu Jiansheng Xie Hongming Pan Weidong Han Wendong Huang |
| author_sort | Wei Zhang |
| collection | DOAJ |
| description | Patients with inflammatory bowel disease are at increased risk for colitis-associated colorectal cancer (CAC). Therefore, controlling intestinal inflammation is a key therapeutic strategy for CAC. MicroRNAs (miRNAs or miRs) are a family of small noncoding RNAs that have the capacity to regulate fundamental biological processes. To date, a number of miRNAs have been identified as critical regulators of inflammation. However, the specific role of miR-26a in colonic inflammation and colitis-associated carcinogenesis is still elusive. Here, we generated mice with miR-26a myeloid-cell-specific overexpression to show that miR-26a suppressed the intestinal inflammatory response in macrophages by decreasing nuclear factor κB (NF-κB)/STAT3 activation and interleukin 6 (IL-6) production. At the molecular level, a number of NF-κB regulators, including TLR3, PTEN, and PKCδ, were identified as potential targets of miR-26a. Our results thus identify a novel miRNA-mediated mechanism that suppresses carcinogenic inflammation in the colon. |
| first_indexed | 2024-04-11T20:19:20Z |
| format | Article |
| id | doaj.art-628afbdb37ca4b37967b9262b5f00a34 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-11T20:19:20Z |
| publishDate | 2021-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-628afbdb37ca4b37967b9262b5f00a342022-12-22T04:04:52ZengElsevierMolecular Therapy: Nucleic Acids2162-25312021-06-0124264273miR-26a attenuates colitis and colitis-associated cancer by targeting the multiple intestinal inflammatory pathwaysWei Zhang0Xianghui Fu1Jiansheng Xie2Hongming Pan3Weidong Han4Wendong Huang5Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang 310016, ChinaDepartment of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA; Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Corresponding author: Xianghui Fu, Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang 310016, ChinaDepartment of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang 310016, ChinaDepartment of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang 310016, China; Department of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA; Corresponding author: Weidong Han, MD, PhD, Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang 310016, China.Department of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA; Graduate School of Biological Science, City of Hope National Medical Center, Duarte, CA 91010, USA; Corresponding author: Wendong Huang, Department of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA.Patients with inflammatory bowel disease are at increased risk for colitis-associated colorectal cancer (CAC). Therefore, controlling intestinal inflammation is a key therapeutic strategy for CAC. MicroRNAs (miRNAs or miRs) are a family of small noncoding RNAs that have the capacity to regulate fundamental biological processes. To date, a number of miRNAs have been identified as critical regulators of inflammation. However, the specific role of miR-26a in colonic inflammation and colitis-associated carcinogenesis is still elusive. Here, we generated mice with miR-26a myeloid-cell-specific overexpression to show that miR-26a suppressed the intestinal inflammatory response in macrophages by decreasing nuclear factor κB (NF-κB)/STAT3 activation and interleukin 6 (IL-6) production. At the molecular level, a number of NF-κB regulators, including TLR3, PTEN, and PKCδ, were identified as potential targets of miR-26a. Our results thus identify a novel miRNA-mediated mechanism that suppresses carcinogenic inflammation in the colon.http://www.sciencedirect.com/science/article/pii/S2162253121000640MiR-26aIntestinal inflammationColitis-associated carcinogenesisNF-κB/STAT3Macrophage |
| spellingShingle | Wei Zhang Xianghui Fu Jiansheng Xie Hongming Pan Weidong Han Wendong Huang miR-26a attenuates colitis and colitis-associated cancer by targeting the multiple intestinal inflammatory pathways Molecular Therapy: Nucleic Acids MiR-26a Intestinal inflammation Colitis-associated carcinogenesis NF-κB/STAT3 Macrophage |
| title | miR-26a attenuates colitis and colitis-associated cancer by targeting the multiple intestinal inflammatory pathways |
| title_full | miR-26a attenuates colitis and colitis-associated cancer by targeting the multiple intestinal inflammatory pathways |
| title_fullStr | miR-26a attenuates colitis and colitis-associated cancer by targeting the multiple intestinal inflammatory pathways |
| title_full_unstemmed | miR-26a attenuates colitis and colitis-associated cancer by targeting the multiple intestinal inflammatory pathways |
| title_short | miR-26a attenuates colitis and colitis-associated cancer by targeting the multiple intestinal inflammatory pathways |
| title_sort | mir 26a attenuates colitis and colitis associated cancer by targeting the multiple intestinal inflammatory pathways |
| topic | MiR-26a Intestinal inflammation Colitis-associated carcinogenesis NF-κB/STAT3 Macrophage |
| url | http://www.sciencedirect.com/science/article/pii/S2162253121000640 |
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