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Paradoxical tumor suppressive role of the musculoaponeurotic fibrosarcoma gene in colorectal cancer

Itakura, H.; Hata, T.; Okuzaki, D.; Takeda, K.; Iso, K.; Qian, Y.; Morimoto, Y.; Adachi, T.; Hirose, H.; Yokoyama, Y.; Ogino, T.; Miyoshi, N.; Takahashi, H.; Uemura, M.; Mizushima, T.; Hinoi, T.; Mori, M.; Doki, Y.; Eguchi, H.; Yamamoto, H.

2022-08-26 molecular biology
10.1101/2022.08.25.505236 bioRxiv
Show abstract

Somatic cell reprogramming using the microRNAs miR200c, 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.

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