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Retinoid acid induced 16 deficiency aggravates colitis and colitis-associated tumorigenesis in mice.

ABSTRACT: Inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC) is a serious health issue, but etiopathological factors remain unclear. Although some studies reported the roles of Retinoid acid induced 16 (RAI16) in the tumorigenesis of hepatocellular carcinoma and PKA signaling, the roles of RAI16 in IBD and CRC are undressed. RAI16^-/- mice were generated and the roles of RAI16 were addressed in dextran sodium sulfate (DSS) or azoxymethane (AOM)-DSS induced IBD or CAC mouse models, respectively. At first, RAI16^-/- mice were viable, fertile with no apparent defects. Then, it was found that RAI16^-/- mice were more susceptibility to colitis induced by DSS than wild type (WT) littermates, which was evaluated by disease activity index and histological score. Furthermore, the expressions of tissues repair associated molecules Cox2, Ereg and MMP-10 were significantly decreased in RAI16^-/- colon under DSS treatment. Gut barrier related genes including antimicrobial peptides Reg3b and Reg3g and intestinal mucus genes Muc4, Muc6 and Muc20 were reduced in RAI16^-/- colon. These findings indicated that RAI16 may function to affect genes involved in intestinal barrier function and immunoprotective inflammation. Accordingly, RAI16^-/- mice displayed significantly increased tumor burden compared with WT mice assessed in CAC model induced by AOM/DSS. Much more Ki67?+?nuclei were observed in RAI16^-/- tumors suggesting RAI16 to be critical in colonic cell proliferation during tumorigenesis. Conclusively, we demonstrate the roles of RAI16 in colonic inflammation and inflammation-associated tumorigenesis by using a novel RAI16^-/- mouse model for the first time.

SUBMITTER: Xu YL

PROVIDER: S-EPMC6925230 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Retinoid acid induced 16 deficiency aggravates colitis and colitis-associated tumorigenesis in mice.

Xu Yu-Lin YL Ding Cui-Ling CL Qian Chun-Lin CL Qi Zhong-Tian ZT Wang Wen W

Cell death & disease 20191220 12

Inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC) is a serious health issue, but etiopathological factors remain unclear. Although some studies reported the roles of Retinoid acid induced 16 (RAI16) in the tumorigenesis of hepatocellular carcinoma and PKA signaling, the roles of RAI16 in IBD and CRC are undressed. RAI16<sup>-/-</sup> mice were generated and the roles of RAI16 were addressed in dextran sodium sulfate (DSS) or azoxymethane (AOM)-DSS induced IBD or CAC ...[more]

PMID: 31862898

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Retinoid acid induced 16 deficiency aggravates colitis and colitis-associated tumorigenesis in mice.

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Retinoid acid induced 16 deficiency aggravates colitis and colitis-associated tumorigenesis in mice.

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