miR-663a regulates growth of colon cancer
cells, after administration of antimicrobial
peptides, by targeting CXCR4-p21 pathway

Kuroda, k; Fukuda, T; Krstic-Demonacos, M; Demonacos, C; Okumura, K; Isogai, H; Hayashi, M; Saito, K; Isogai, E

Abstract

Abstract
Background: Antimicrobial peptides (AMPs) play important roles in the innate immune system of all life forms and
recently have been characterized as multifunctional peptides that have a variety of biological roles such as anticancer
agents. However, detailed mechanism of antimicrobial peptides on cancer cells is still largely unknown.
Methods: miRNA array and real-time qPCR were performed to reveal the behavior of miRNA in colon cancer HCT116
cells during the growth suppression induced by the AMPs. Establishment of miR-663a over-expressing HCT116 cells
was carried out for the evaluation of growth both in vitro and in vivo. To identify the molecular mechanisms, we used
western blotting analysis.
Results: miR-663a is upregulated by administration of the human cathelicidin AMP, LL-37, and its analogue peptide,
FF/CAP18, in the colon cancer cell line HCT116. Over-expression of miR-663a caused anti-proliferative effects both in
vitro and in vivo. We also provide evidence supporting the view that these effects are attributed to suppression of the
expression of the chemokine receptor CXCR4, resulting in the abrogation of phosphorylation of Akt and cell cycle
arrest in G2/M via p21 activation.
Conclusions: This study contributes to the understanding of the AMPs’ mediated anti-cancer mechanisms in colon
cancer cells and highlights the possibility of using AMPs and miRNAs towards developing future strategies for cancer
therapy.

Citation

peptides, by targeting CXCR4-p21 pathway. BMC Cancer, 17, 33-43. https://doi.org/10.1186/s12885-016-3003-9

• Journal Article Type: Article
• Acceptance Date: Dec 15, 2016
• Publication Date: Jan 7, 2017
• Deposit Date: Jan 16, 2017
• Publicly Available Date: Jan 16, 2017
• Journal: BMC Cancer
• Electronic ISSN: 1471-2407
• Publisher: Springer Verlag
• Volume: 17
• Pages: 33-43
• DOI: https://doi.org/10.1186/s12885-016-3003-9
• Publisher URL: http://dx.doi.org/10.1186/s12885-016-3003-9
• Related Public URLs: http://bmccancer.biomedcentral.com/
• Additional Information: Funders : Collaborators work was funded by:Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) [2013-2016: Grant Number 25292178, 2016-2018: Grant Number 16H05036, and 2014-2017: Grant Number26·5415