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TRIM22 inhibits endometrial cancer progression through the NOD2/NF??B signaling pathway and confers a favorable prognosis.

ABSTRACT: Endometrial cancer (EnC) is a malignant gynecological tumor commonly observed in developed countries, specifically among post?menopausal women. Although numerous patients with EnC receive promising prognoses, those with advanced or metastatic disease often have a poor prognosis and an impaired quality of life. Tripartite motif?containing 22 (TRIM22) has been confirmed to play many crucial roles in different biological processes, from inflammatory to tumorigenesis. However, the multifaceted roles of TRIM22 in EnC remain uncharacterized. Herein, comparing normal endometrial tissues with tumor tissues obtained from patients, it was concluded that TRIM22 expression was decreased in tumor tissues. However, the overexpression of TRIM22 served to inhibit the migratory, invasive, proliferative and cell cycle activity of EnC cells. Moreover, the knockdown of TRIM22 increased the migratory, invasive, and proliferative activity of the EnC cells. Furthermore, it was found that TRIM22 effectively suppressed EnC progression through the nucleotide binding oligomerization domain containing 2 (NOD2)/nuclear factor (NF)??B pathway. The data also demonstrated that TRIM22 functions as an inhibitor of EnC tumor xenograft growth in vivo. Overall, the findings of the present study define a novel regulatory role for TRIM22 in EnC progression. Moreover, TRIM22 may serve as an important prognostic predictor for EnC.

SUBMITTER: Zhang L

PROVIDER: S-EPMC7115357 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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TRIM22 inhibits endometrial cancer progression through the NOD2/NF‑κB signaling pathway and confers a favorable prognosis.

Zhang Liping L Zhang Bingqian B Wei Muyun M Xu Zhen Z Kong Weiya W Deng Ke K Xu Xinxin X Zhang Lin L Ζhao Xingbo X Yan Lei L

International journal of oncology 20200304 5

Endometrial cancer (EnC) is a malignant gynecological tumor commonly observed in developed countries, specifically among post‑menopausal women. Although numerous patients with EnC receive promising prognoses, those with advanced or metastatic disease often have a poor prognosis and an impaired quality of life. Tripartite motif‑containing 22 (TRIM22) has been confirmed to play many crucial roles in different biological processes, from inflammatory to tumorigenesis. However, the multifaceted roles ...[more]

PMID: 32319602

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Project description:Severe forms of inflammatory bowel disease (IBD) that develop in very young children can be caused by variants in a single gene. We performed whole-exome sequence (WES) analysis to identify genetic factors that might cause granulomatous colitis and severe perianal disease, with recurrent bacterial and viral infections, in an infant of consanguineous parents.We performed targeted WES analysis of DNA collected from the patient and her parents. We validated our findings by a similar analysis of DNA from 150 patients with very-early-onset IBD not associated with known genetic factors analyzed in Toronto, Oxford, and Munich. We compared gene expression signatures in inflamed vs noninflamed intestinal and rectal tissues collected from patients with treatment-resistant Crohn's disease who participated in a trial of ustekinumab. We performed functional studies of identified variants in primary cells from patients and cell culture.We identified a homozygous variant in the tripartite motif containing 22 gene (TRIM22) of the patient, as well as in 2 patients with a disease similar phenotype. Functional studies showed that the variant disrupted the ability of TRIM22 to regulate nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-?B. Computational studies demonstrated a correlation between the TRIM22-NOD2 network and signaling pathways and genetic factors associated very early onset and adult-onset IBD. TRIM22 is also associated with antiviral and mycobacterial effectors and markers of inflammation, such as fecal calprotectin, C-reactive protein, and Crohn's disease activity index scores.In WES and targeted exome sequence analyses of an infant with severe IBD characterized by granulomatous colitis and severe perianal disease, we identified a homozygous variant of TRIM22 that affects the ability of its product to regulate NOD2. Combined computational and functional studies showed that the TRIM22-NOD2 network regulates antiviral and antibacterial signaling pathways that contribute to inflammation. Further study of this network could lead to new disease markers and therapeutic targets for patients with very early and adult-onset IBD.

Dataset Information

TRIM22 inhibits endometrial cancer progression through the NOD2/NF??B signaling pathway and confers a favorable prognosis.

Publications

TRIM22 inhibits endometrial cancer progression through the NOD2/NF‑κB signaling pathway and confers a favorable prognosis.

Similar Datasets

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