Interference with GINS2 inhibits ovarian cancer cell cycle entry by degrading CyclinA2 through ubiquitination

The abnormal regulation of the cell cycle in tumor cells is linked to their proliferation, drug resistance, and recurrence. However, the mechanisms behind cell cycle regulation still need to be revealed for malignant tumor treatment. In this study, we conducted a bioinformatics analysis on the ovarian tissue mRNA microarray datasets from the GEO database. It revealed the involvement of GINS complex subunit 2 (GINS2), one of the main components of CMG helicase, not only in DNA replication, but also in cell cycle regulation. Experimental verification showed that GINS2 was regulated by cell cycle transcription factor E2F1 and could, in turn, improve the expression of Cyclin A2, promoting the transformation of cell cycle G1/S phase and the proportion of S phase. Surprisingly, GINS2 affected Cyclin A2 expression via ubiquitin degradation of MCM7 independent of the P53 and P27-associated extranuclear pathways. These findings emphasize GINS2's significance in the functional regulation of CMG helicase. The study concludes that GINS2 is a key player in the direct feedback up-regulation of the cell cycle through affecting Cyclin A2 expression, providing new insights into cell cycle regulation mechanisms.