Norepinephrine‐CREB1‐miR‐373 axis promotes progression of colon cancer
The adrenergic system contributes to the stress‐induced onset and progression of cancer. Adrenergic fibers are the primary source of norepinephrine (NE). The underlying mechanisms involved in NE‐induced colon cancer remain to be understood. In this study, we describe the function and regulatory netw...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-05-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12657 |
| _version_ | 1828855909542002688 |
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| author | Jia Han Qiuyu Jiang Ruili Ma Huahua Zhang Dongdong Tong Kaijie Tang Xiaofei Wang Lei Ni Jiyu Miao Baojun Duan Yang Yang Yanke Chen Fei Wu Jiming Han Mengchang Wang Ni Hou Chen Huang |
| author_facet | Jia Han Qiuyu Jiang Ruili Ma Huahua Zhang Dongdong Tong Kaijie Tang Xiaofei Wang Lei Ni Jiyu Miao Baojun Duan Yang Yang Yanke Chen Fei Wu Jiming Han Mengchang Wang Ni Hou Chen Huang |
| author_sort | Jia Han |
| collection | DOAJ |
| description | The adrenergic system contributes to the stress‐induced onset and progression of cancer. Adrenergic fibers are the primary source of norepinephrine (NE). The underlying mechanisms involved in NE‐induced colon cancer remain to be understood. In this study, we describe the function and regulatory network of NE in the progression of colon cancer. We demonstrate that NE‐induced phosphorylation of cAMP response element‐binding protein 1 (CREB1) promotes proliferation, migration, and invasion of human colon cancer cells. The downstream effector of NE, CREB1, bound to the promoter of miR‐373 and transcriptionally activated its expression. miR‐373 expression was shown to be necessary for NE‐induced cell proliferation, invasion, and tumor growth. We confirmed that proliferation and invasion of colon cancer cells are regulated in vitro and in vivo by miR‐373 through targeting of the tumor suppressors TIMP2 and APC. Our data suggest that NE promotes colon cancer cell proliferation and metastasis by activating the CREB1–miR‐373 axis. The study of this novel signaling axis may provide mechanistic insights into the neural regulation of colon cancer and help in the design of future clinical studies on stress biology in colorectal cancer. |
| first_indexed | 2024-12-13T01:03:35Z |
| format | Article |
| id | doaj.art-4f4421baac1941bf9ef286b404252655 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-13T01:03:35Z |
| publishDate | 2020-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-4f4421baac1941bf9ef286b4042526552022-12-22T00:04:37ZengWileyMolecular Oncology1574-78911878-02612020-05-011451059107310.1002/1878-0261.12657Norepinephrine‐CREB1‐miR‐373 axis promotes progression of colon cancerJia Han0Qiuyu Jiang1Ruili Ma2Huahua Zhang3Dongdong Tong4Kaijie Tang5Xiaofei Wang6Lei Ni7Jiyu Miao8Baojun Duan9Yang Yang10Yanke Chen11Fei Wu12Jiming Han13Mengchang Wang14Ni Hou15Chen Huang16Department of Cell Biology and Genetics School of Basic Medical Sciences Xi’an Jiaotong University Health Science Center ChinaDepartment of Cell Biology and Genetics School of Basic Medical Sciences Xi’an Jiaotong University Health Science Center ChinaSchool of Basic Medical Science Xi’an Medical University ChinaMedical College Yan'an University ChinaDepartment of Cell Biology and Genetics School of Basic Medical Sciences Xi’an Jiaotong University Health Science Center ChinaDepartment of Cell Biology and Genetics School of Basic Medical Sciences Xi’an Jiaotong University Health Science Center ChinaDepartment of Cell Biology and Genetics School of Basic Medical Sciences Xi’an Jiaotong University Health Science Center ChinaDepartment of Cell Biology and Genetics School of Basic Medical Sciences Xi’an Jiaotong University Health Science Center ChinaDepartment of Cell Biology and Genetics School of Basic Medical Sciences Xi’an Jiaotong University Health Science Center ChinaDepartment of Medical Oncology The Third Affiliated Hospital to Xi'an Jiaotong University ChinaDepartment of Health Toxicology and Hygiene Inspection School of Public Health Xi'an Jiaotong University Health Science Center ChinaDepartment of Cell Biology and Genetics School of Basic Medical Sciences Xi’an Jiaotong University Health Science Center ChinaDepartment of Cell Biology and Genetics School of Basic Medical Sciences Xi’an Jiaotong University Health Science Center ChinaMedical College Yan'an University ChinaDepartment of Hematology The First Hospital Affiliated to Xi'an Jiaotong University ChinaDepartment of Cell Biology and Genetics School of Basic Medical Sciences Xi’an Jiaotong University Health Science Center ChinaDepartment of Cell Biology and Genetics School of Basic Medical Sciences Xi’an Jiaotong University Health Science Center ChinaThe adrenergic system contributes to the stress‐induced onset and progression of cancer. Adrenergic fibers are the primary source of norepinephrine (NE). The underlying mechanisms involved in NE‐induced colon cancer remain to be understood. In this study, we describe the function and regulatory network of NE in the progression of colon cancer. We demonstrate that NE‐induced phosphorylation of cAMP response element‐binding protein 1 (CREB1) promotes proliferation, migration, and invasion of human colon cancer cells. The downstream effector of NE, CREB1, bound to the promoter of miR‐373 and transcriptionally activated its expression. miR‐373 expression was shown to be necessary for NE‐induced cell proliferation, invasion, and tumor growth. We confirmed that proliferation and invasion of colon cancer cells are regulated in vitro and in vivo by miR‐373 through targeting of the tumor suppressors TIMP2 and APC. Our data suggest that NE promotes colon cancer cell proliferation and metastasis by activating the CREB1–miR‐373 axis. The study of this novel signaling axis may provide mechanistic insights into the neural regulation of colon cancer and help in the design of future clinical studies on stress biology in colorectal cancer.https://doi.org/10.1002/1878-0261.12657colorectal cancerCREB1miR‐373NETIMP2 |
| spellingShingle | Jia Han Qiuyu Jiang Ruili Ma Huahua Zhang Dongdong Tong Kaijie Tang Xiaofei Wang Lei Ni Jiyu Miao Baojun Duan Yang Yang Yanke Chen Fei Wu Jiming Han Mengchang Wang Ni Hou Chen Huang Norepinephrine‐CREB1‐miR‐373 axis promotes progression of colon cancer Molecular Oncology colorectal cancer CREB1 miR‐373 NE TIMP2 |
| title | Norepinephrine‐CREB1‐miR‐373 axis promotes progression of colon cancer |
| title_full | Norepinephrine‐CREB1‐miR‐373 axis promotes progression of colon cancer |
| title_fullStr | Norepinephrine‐CREB1‐miR‐373 axis promotes progression of colon cancer |
| title_full_unstemmed | Norepinephrine‐CREB1‐miR‐373 axis promotes progression of colon cancer |
| title_short | Norepinephrine‐CREB1‐miR‐373 axis promotes progression of colon cancer |
| title_sort | norepinephrine creb1 mir 373 axis promotes progression of colon cancer |
| topic | colorectal cancer CREB1 miR‐373 NE TIMP2 |
| url | https://doi.org/10.1002/1878-0261.12657 |
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