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Aberrant expression of MYD88 via RNA-controlling CNOT4 and EXOSC3 in colonic mucosa impacts generation of colonic cancer

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Title: Aberrant expression of MYD88 via RNA-controlling CNOT4 and EXOSC3 in colonic mucosa impacts generation of colonic cancer
Authors: Tsuda, Masumi Browse this author →KAKEN DB
Noguchi, Misa Browse this author
Kurai, Tsuyoshi Browse this author
Ichihashi, Yuji Browse this author
Ise, Koki Browse this author
Wang, Lei Browse this author
Ishida, Yusuke Browse this author
Tanino, Mishie Browse this author
Hirano, Satoshi Browse this author →KAKEN DB
Asaka, Masahiro Browse this author
Tanaka, Shinya Browse this author →KAKEN DB
Keywords: CNOT4
colon cancer
preventive medicine
RNA control
Issue Date: 5-Dec-2021
Publisher: John Wiley & Sons
Journal Title: Cancer science
Volume: 112
Issue: 12
Start Page: 5100
End Page: 5113
Publisher DOI: 10.1111/cas.15157
Abstract: In 2020, the worldwide incidence and mortality of colorectal cancer (CRC) were third and second, respectively. As the 5-y survival rate is low when CRC is diagnosed at an advanced stage, a reliable method to predict CRC susceptibility is important for preventing the onset and development and improving the prognosis of CRC. Therefore, we focused on the normal colonic mucosa to investigate changes in gene expression that may induce subsequent genetic alterations that induce malignant transformation. Comprehensive gene expression profiling in the normal mucosa adjacent to colon cancer (CC) compared with tissue from non-colon cancer patients was performed. PCR arrays and qRT-PCR revealed that the expression of 5 genes involved in the immune response, including MYD88, was increased in the normal mucosa of CC patients. The expression levels of MYD88 were strikingly increased in precancerous normal mucosa specimens, which harbored no somatic mutations, as shown by immunohistochemistry. Microarray analysis identified 2 novel RNA-controlling molecules, EXOSC3 and CNOT4, that were significantly upregulated in the normal mucosa of CC patients and were clearly visualized in the nuclei. Forced expression of EXOSC3 and CNOT4 in human colonic epithelial cells increased the expression of IFNGR1, MYD88, NF kappa BIA, and STAT3 and activated ERK1/2 and JNK in 293T cells. Taken together, these results suggested that, in the inflamed mucosa, EXOSC3- and CNOT4-mediated RNA stabilization, including that of MYD88, may trigger the development of cancer and can serve as a potential predictive marker and innovative treatment to control cancer development.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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