Top2a, also known as topoisomerase II alpha, is a crucial enzyme in DNA replication and transcription. It plays a vital role in relieving topological stress during DNA processes, ensuring the normal progress of cell division. Top2a is involved in multiple pathways, such as the AKT/mTOR, Wnt/β -catenin, and NF -κB signaling pathways, and is of great biological importance in cell proliferation, cell cycle regulation, and maintaining genome stability [1,2,4]. Genetic models, like KO/CKO mouse models, are valuable for studying Top2a's functions.

In ovarian cancer, Top2a knockdown inhibits cell proliferation, leading to G1 phase arrest and apoptosis, and it is confirmed to regulate cell processes through the AKT/mTOR pathway [1]. In medulloblastoma, knockdown of Top2a suppresses cell proliferation, migration, invasion, and radioresistance, with the Wnt/β -catenin signaling pathway involved [2]. In hepatocellular carcinoma, inhibition of Top2a can reverse drug resistance to regorafenib [3]. In recurrent implantation failure, TOP2A -deficient mice show lower fetal weights, and TOP2A affects decidualization through the NF -κB pathway [4].

In conclusion, Top2a is essential for DNA -related cellular functions. Model -based research, especially KO/CKO mouse models, has revealed its significance in various disease areas, including ovarian cancer, medulloblastoma, hepatocellular carcinoma, and recurrent implantation failure. Understanding Top2a's functions provides insights into disease mechanisms and potential therapeutic strategies.