Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 626, Issue -, Pages 220-228Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.08.036
Keywords
?-catenin; Colorectal carcinoma; Wnt
Categories
Funding
- Shaanxi Province Technology Innovation Guidance Special Project -Regional Innovation Capa- bility Guidance Program [2022QFY01-08]
- Science and Technology Talents Support Program of Shaanxi Provincial People's Hospital [2021BJ-19]
- Shaanxi Province Key Research and Development Plan [2021SF-306]
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The study demonstrates a cancer-suppressive function of CAMK2N1 in colorectal carcinoma, exerting tumor-inhibiting effects via suppression of the Wnt/β-catenin pathway.
The deregulation of calcium/calmodulin-dependent protein kinase II inhibitor 1 (CAMK2N1) is linked to the carcinogenesis reported in several malignancies. To date, studies describing the role of CAMK2N1 in colorectal carcinoma are scarce. The current project was carried out to study the relationship between CAMK2N1 and colorectal carcinoma progression. CAMK2N1 levels were lowered in colorectal carcinoma tissue, which also correlated to poor overall survival in patients. Colorectal carcinoma cell lines with overexpressed CAMK2N1 showed a reduction in transformative phenotypes, including proliferation suppression, the blocking of cell cycle progression, metastasis inhibition and chemoresistance reduction, whereas CAMK2N1-silenced cells showed the opposite effect. Mechanistic studies revealed a novel regulatory role of CAMK2N1 on Wnt/f3-catenin transduction. Up-regulation of CAMK2N1 lowered the level of disheveled 2, phosphorylated GSK-3f3, f3-catenin, c-myc and cyclin D1. Re-expression of f3-catenin decreased the CAMK2N1-mediated tumor-inhibiting effects. Moreover, blocking of Wnt/f3-catenin diminished CAMK2N1-silencing-elicited cancer-enhancing effect. Critically, the tumorigenicity of CAMK2N1-overexpressed cells was markedly weakened in nude mice. To conclude, the study demon-strated a cancer-suppressive function of CAMK2N1 in colorectal carcinoma and illustrated that CAMK2N1 exerts the tumor-inhibiting effects via suppression of the Wnt/f3-catenin pathway.(c) 2022 Elsevier Inc. All rights reserved.
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