Overexpression of Tripartite Motif Containing 37 Induces Cisplatin Resistance to Ovarian Carcinoma and Activates the Wnt/β-Catenin Signaling Pathway

Abstract

Background: Expression confusion of tripartite motif (TRIM) family proteins has been associated with various cellular processes such as immune disorders, neurological-related diseases, protein degradation, and tumorigenesis. Therefore, we aim to explore the function and clinical significance of TRIM family proteins in chemotherapy resistance in ovarian cancer. Methods: Western blot analysis and immunohistochemistry (IHC) assay were conducted to assess the protein expression levels of TRIM37 in both ovarian cancer cell lines and patient tissues. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were conducted to detect the effect of TRIM37 on 50% inhibitory concentration (IC₅₀). The rate of apoptotic cells was conducted using fluorescence-activated cell sorting (FACS) assays. Moreover, Luciferase assays were performed to detect the luciferase reporter activity. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were conducted to detect the pro-cancer effect of TRIM37. Results: We found that TRIM37 was increased in ovarian cancer tissues, showing partial response to cisplatin chemotherapy (p < 0.01). The high TRIM37 expression was linked to a worse overall survival prognosis and lower disease-free survival rate in our cancer tissue samples and public ovarian cancer databases (p < 0.001, p < 0.01). Functionally, overexpression of TRIM37 endows cisplatin resistance in ovarian cancer cells. However, inhibition of TRIM37 counteracted this resistance in ovarian cancer. Additionally, TRIM37 was found to activate the wnt/β-catenin signaling pathway. Conclusions: Our findings indicate that TRIM37 contributes to enhanced cisplatin resistance in ovarian cancer, suggesting its potential as a promising chemotherapy biomarker.