TRIM22 Inhibits Endometrial Cancer Progression Through The NOD2/NF-κB Signaling Pathway And Confers Favorable Prognosis

Chapter 1.TRIM22 Inhibits Endometrial Cancer Progression through the NOD2/NF-κB Signaling Pathway and Confers Favorable PrognosisObjective:Endometrial cancer(EnC)is a malignant gynecologic tumor,those of advanced or metastatic disease are often poor and impair quality of life.TRIM22 has been confirmed to play many important roles in different biological processes,from inflammatory to tumorigenesis.However,the multifaceted roles of TRIM22 in EnC remain uncharacterized.Methods:TRIM22 expression was analyzed by IHC in normal endometrial tissues and tumor tissues;8 pairs of matching adjacent and tumor tissues derived from EnC patients were sent for western blot.The role of TRIM22 in the EnC progression were examined by upregulation/downregulation of TRIM22 in EnC both in vitro and in vivo.Results:comparing normal endometrial tissues with tumor tissues obtained from human 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.Conclusions:Overall,our study defines a novel regulatory role for TRIM22 in EnC progression.Moreover,TRIM22 may serve as an important prognostic predictor for EnC.Chapter 2.TRIM22 Expression May Be Associated with Efficient Progestin Therapy in Atypical Endometrial HyperplasiaObjective:To investigate the relationship between the efficacy of progesterone therapy and TRIM22 expression in atypical endometrial hyperplasia patients,and the possible role of TRIM22 in reversing atypical endometrial hyperplasia.Methods:Immunohistochemistry was used to detect the expression of TRIM22 in atypical endometrial hyperplasia tissues pretherapy and post-treatment with high dose progestin.The expression of TRIM22 in endometrial cancer cells pretreated with different concentration progesterone was detected by western blotting.The influence of TRIM22 on the proliferation ability of endometrial cancer cells was detected by CCK8 assay.Results:In the progestin sensitive group,TRIM22 expression increased after progestin treatment(P=0.0003).However,in the progestin insensitive group,the expression of TRIM22 was no difference between pretherapy.and post-treatment with progestin(P=0.6349).The TRIM22 expression increased dose-dependently with different progestin concentrations,but the proliferation ability decreased.Conclusions:The efficacy of progesterone in treating atypical endometrial hyperplasia is associated with increased expression of TRIM22,probably,TRIM22 reverses atypical endometrial hyperplasia through inhibiting the proliferation of endometrial cells.