TRIM22 inhibits endometrial cancer progression through the NOD2/NF‑κB 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)-κB 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.

Prognostic Immune-Related Analysis Based on Differentially Expressed Genes in Left- and Right-Sided Colon Adenocarcinoma

“…It is confirmed that the TRIM22 played many crucial roles in different biological processes, from inflammatory to tumorigenesis. In endometrial cancer, TRIM22 is proven to inhibit tumor growth by NF-κB signaling pathway, and conferred a favorable prognosis ( 44 ). CIITA is the regulator of the major histocompatibility complex gene expression ( 45 ).…”

TRIMming Down Hormone-Driven Cancers: The Biological Impact of TRIM Proteins on Tumor Development, Progression and Prognostication

“…Four TRIM proteins have been related to EC: TRIM22, TRIM25, TRIM27 and TRIM44 [ 157 , 158 , 159 , 160 , 161 , 162 ]. TRIM22 expression was reported to be downregulated in EC samples compared to normal endometrial tissues, and low TRIM22 expression was found to be associated with a high clinical stage of the disease [ 157 ]. In the same study, TRIM22 decreased proliferation and migration of KLE, Ishikawa and RL-952 EC cells in vitro and inhibited tumor growth in xenograft models in vivo [ 157 ].…”

“…TRIM22 expression was reported to be downregulated in EC samples compared to normal endometrial tissues, and low TRIM22 expression was found to be associated with a high clinical stage of the disease [ 157 ]. In the same study, TRIM22 decreased proliferation and migration of KLE, Ishikawa and RL-952 EC cells in vitro and inhibited tumor growth in xenograft models in vivo [ 157 ]. These effects are explained by increased levels of the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) protein upon TRIM22 overexpression in Ishikawa cells [ 157 ].…”

“…In the same study, TRIM22 decreased proliferation and migration of KLE, Ishikawa and RL-952 EC cells in vitro and inhibited tumor growth in xenograft models in vivo [ 157 ]. These effects are explained by increased levels of the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) protein upon TRIM22 overexpression in Ishikawa cells [ 157 ]. The role of NOD2 in cancer is controversial and may depend on the type of cancer considered.…”

“…However, NOD2 has been involved in the regulation of numerous cellular pathways including NF-κB-, PI3K- and MAPK-cascades [ 163 ]. In the study published by Zhang and coworkers, TRIM22 increased not only NOD2 protein levels but also the protein levels of NF-κB-p65 and IκBα, while their phosphorylation was reduced, resulting in diminished NF-κB signaling [ 157 ]. As a parallel effect, TRIM22 also inhibited the activity of NF-κB by preventing the translocation of the p65 subunit into the nucleus.…”