Roles of increased NUCKS1 expression in endometriosis

Abstract

Background Endometriosis is still a difficult problem for women. The Nuclear Ubiquitous Casein and cyclin-dependent Kinase Substrate 1 (NUCKS1) gene is located on human chromosome 1q32.1. It encodes the NUCKS1 protein, a 27 kDa nuclear DNA binding protein that plays an important role in cell growth and proliferation. NUCKS1 plays an important role in the development of many diseases. However, its role in endometriosis is unclear. Methods Ectopic endometrial tissues and normal tissue specimens were collected, and the expression of NUCKS1, NF-κB and PI3K was detected by RT-qPCR and immunohistochemistry. Inhibition of NUCKS1 in hEM15A cells, study the changes in cell viability, apoptosis, migration and protein expression by CCK8 assay, flow cytometry, wound-healing assay, western blot and ELISA techniques. The comparison of differences between the two groups was implemented using unpaired sample t test or Mann-whitney U test. One-way analysis of variance or Kruskal-wallis test was used for comparisons among the three groups. Results (1) NUCKS1 is highly expressed in endometriosis tissues. (2) Inhibition of NUCKS1 decreases cell viability and capability of migration, and increases apoptosis in endometriosis cells. (3) Expressions of NF-κB and PI3K are increased in endometriosis tissues, and inhibition of NUCKS1 decreases the expression levels of PI3K and NF-κB in endometriosis cells. (4) Inhibition of NUCKS1 decreases the expression of VEGF. Conclusion (1) NUCKS1 is overexpressed in endometriosis, and inhibition of NUCKS1 inhibits cell viability and capability of migration, and increases apoptosis. (2) NUCKS1 promotes the progress of endometriosis through activating PI3K and NF-κB pathways, and VEFG is also involved in this process.

Role of Cyclins and Cytoskeletal Proteins in Endometriosis: Insights into Pathophysiology

“…NUCKS1 exhibits elevated expression levels in ectopic endometrium-like tissues. In vitro studies have revealed that inhibiting NUCKS1 significantly impairs cell proliferation and induces apoptosis in these tissues [71]. Considering the complexity of cyclin B1's role in the proliferation of endometrial cells, it is essential to recognize that increased expression in diseased tissue does not necessarily imply it is the primary factor driving cell proliferation in the specific disease under investigation.…”

“…The interconnection between NUCKS1, cyclin expression, and the previously discussed relationship highlights its indirect involvement in the regulation of cell cycle processes. This intricate network implicates both cyclins and CDKs in these cellular mechanisms [71].…”