Top2a, also known as DNA topoisomerase II alpha, is a key catalytic enzyme in DNA replication and cell proliferation [4]. It is involved in various biological processes and associated with multiple pathways. For instance, it plays a role in resolving topological barriers during replication fork reversal, and is part of the ZATT-TOP2A-PICH axis which promotes genome stability [3].

In ovarian cancer, TOP2A knockdown inhibits cell proliferation, arrests cells in the G1 phase, and induces apoptotic death, and it is confirmed to regulate cell proliferation and cell cycle through the AKT/mTOR pathway [1]. In hepatocellular carcinoma, inhibition of TOP2A and EZH2 induces cellular senescence and inhibits cell proliferation, with EZH2 promoting TOP2A expression by regulating the H3K27me3-mediated epigenetic silencing of miR-139-5p [2]. In medulloblastoma, knockdown of TOP2A inhibits cell proliferation, migration, and invasion, and suppresses radioresistance, with the Wnt/β-catenin signaling pathway potentially involved in its mechanisms [4]. In hepatocellular carcinoma, silencing TOP2A enhances cells' sensitivity to regorafenib, and its inhibition by doxorubicin or epirubicin synergizes with regorafenib to suppress tumor growth [5]. In recurrent implantation failure, TOP2A deficit-induced abnormal decidualization leads to the condition via the NF-κB signaling pathway [6]. In recurrent spontaneous abortion, lower TOP2A expression inhibits trophoblast cell proliferation, migration, and invasion by activating the FOXO signaling pathway, and TOP2A inhibition impairs pre-implantation embryo development in mice [7].

In conclusion, Top2a is essential for DNA replication and cell proliferation. Through gene knockout or knockdown studies in various models, its role in multiple disease conditions such as cancers and reproductive disorders has been revealed. These findings help in understanding the underlying molecular mechanisms and may potentially lead to the development of novel therapeutic strategies targeting Top2a.