NRDR Inhibits the Migration of Endometrial Cancer Cells and Affects Their Gene Expression

Introduction: Studying the pathogenesis of endometrial cancer is important to treatment of endometrial cancer. NADP(H)-dependent retinol dehydrogenase/reductase (NRDR) is associated with the development of cancer. Our previous research has found that NRDR can inhibit the synthesis of estradiol (E2) in granulosa cells. Based on the above statement, we speculate that NRDR may also be involved in the development of endometrial cancer. Therefore, this study investigated the expression patterns and mechanisms of NRDR in endometrial cancer. Material and Methods: This study was performed using Ishikawa cells combined with multiple methods, including immunohistochemical staining, wound healing and Transwell migration assays, RNA-seq analysis, and so on. Results: The results showed that NRDR was expressed in endometrial cancer tissues and uterine glands, and it was higher in endometrial cancer tissues of elderly patients. Wound healing assay and Transwell migration assay results showed that RNA interference targeting NRDR gene expression could promote the migration of endometrial cancer cells and the expression of α-SMA, Vimentin, and Twist. In addition, E2 could downregulate the expression of NRDR in endometrial cancer cells. Lastly, RNA-seq was performed on Ishikawa cells (RNA interference of NRDR), and the differentially expressed genes (DEGs) were analyzed. Further enrichment analysis of the functions and signaling pathways of DEGs using GO and KEGG revealed that DEGs were mainly enriched in intrinsic component of plasma membrane, integral components of plasma membrane and calcium signaling pathway. Conclusions: In our study, it turns out that NRDR is a tumor suppressor in endometrial cancer cells. Through investigating the physiological function and molecular mechanism of NRDR in endometrial cancer, our experiment provides a theoretical basis for further understanding the pathogenesis of endometrial cancer.