학술논문
Tumor-suppressive role of the musculoaponeurotic fibrosarcoma gene in colorectal cancer
Document Type
article
Author
Hiroaki Itakura; Tsuyoshi Hata; Daisuke Okuzaki; Koki Takeda; Kenji Iso; Yamin Qian; Yoshihiro Morimoto; Tomohiro Adachi; Haruka Hirose; Yuhki Yokoyama; Takayuki Ogino; Norikatsu Miyoshi; Hidekazu Takahashi; Mamoru Uemura; Tsunekazu Mizushima; Takao Hinoi; Masaki Mori; Yuichiro Doki; Hidetoshi Eguchi; Hirofumi Yamamoto
Source
iScience, Vol 26, Iss 4, Pp 106478- (2023)
Subject
Language
English
ISSN
2589-0042
Abstract
Summary: Somatic cell reprogramming using the microRNAs miR-200c, miR-302s, and miR-369s leads to increased expression of cyclin-dependent kinase inhibitors in human colorectal cancer (CRC) cells and suppressed tumor growth. Here, we investigated whether these microRNAs inhibit colorectal tumorigenesis in CPC;Apc mice, which are prone to colon and rectal polyps. Repeated administration of microRNAs inhibited polyp formation. Microarray analysis indicated that c-MAF, which reportedly shows oncogene-like behavior in multiple myeloma and T cell lymphoma, decreased in tumor samples but increased in microRNA-treated normal mucosa. Immunohistochemistry identified downregulation of c-MAF as an early tumorigenesis event in CRC, with low c-MAF expression associated with poor prognosis. Of note, c-MAF expression and p53 protein levels were inversely correlated in CRC samples. c-MAF knockout led to enhanced tumor formation in azoxymethane/dextran sodium sulfate–treated mice, with activation of cancer-promoting genes. c-MAF may play a tumor-suppressive role in CRC development.