Top2a-KO Mouse

TOP2A, also known as topoisomerase II alpha, is an enzyme crucial for DNA replication and cell proliferation. It plays a significant role in resolving topological problems during DNA replication, ensuring the proper segregation of replicated chromosomes. TOP2A is associated with several signaling pathways, such as the AKT/mTOR pathway, and its dysregulation has implications for various biological processes and diseases [1,3].

In ovarian cancer, TOP2A knockdown inhibited cell proliferation, with cells arresting in the G1 phase and undergoing apoptosis, and it was confirmed to regulate cell proliferation and the cell cycle through the AKT/mTOR pathway activity. Mouse model experiments further affirmed its role as a driver of ovarian cancer cell proliferation [1].

In hepatocellular carcinoma, inhibition of EZH2 and TOP2A in vitro induced cellular senescence and inhibited cell proliferation, and in vivo knockdown of EZH2 and TOP2A inhibited tumorigenesis by inducing cellular senescence. EZH2 promotes TOP2A expression by regulating the H3K27me3-mediated epigenetic silencing of miR-139-5p [2].

In medulloblastoma, knockdown of TOP2A inhibited cell proliferation, migration, and invasion, and suppressed radioresistance, with the Wnt/β-catenin signaling pathway potentially involved in these molecular mechanisms [4].

In hepatocellular carcinoma, silencing TOP2A enhanced cells' sensitivity to regorafenib, and inhibition of TOP2A by doxorubicin or epirubicin synergized with regorafenib to suppress the growth of sorafenib-resistant tumors [5].

In recurrent implantation failure, TOP2A deficit-induced abnormal decidualization led to the condition via the NF-κB signaling pathway [6].

In recurrent spontaneous abortion, TOP2A knockdown decreased the proliferation, migration, and invasion of trophoblast cell lines, increased apoptosis, and activated the FOXO signaling pathway, and in vivo inhibition of TOP2A impaired trophectoderm differentiation and embryonic development in mice [7].

In conclusion, TOP2A is essential for DNA replication and cell proliferation. Studies using gene knockout models in various disease conditions, including ovarian cancer, hepatocellular carcinoma, medulloblastoma, recurrent implantation failure, and recurrent spontaneous abortion, have revealed its role in promoting cancer cell growth, affecting radioresistance, and influencing processes related to pregnancy. These findings provide insights into potential therapeutic strategies targeting TOP2A in these diseases.