Open AccessNorepinephrine‐CREB1‐miR‐373 axis promotes progression of colon cancer
Author(s) -
Han Jia,
Jiang Qiuyu,
Ma Ruili,
Zhang Huahua,
Tong Dongdong,
Tang Kaijie,
Wang Xiaofei,
Ni Lei,
Miao Jiyu,
Duan Baojun,
Yang Yang,
Chen Yanke,
Wu Fei,
Han Jiming,
Wang Mengchang,
Hou Ni,
Huang Chen
Publication year - 2020
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12657
Subject(s) - creb1 , colorectal cancer , cancer research , cell growth , metastasis , cancer , biology , creb , effector , cancer cell , microbiology and biotechnology , medicine , endocrinology , transcription factor , biochemistry , gene
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.