RAD21, also known as KIAA0078, NXP1, HR21, Mcd1, Scc1, is an essential gene encoding a DNA double-strand break (DSB) repair protein conserved across eukaryotes [2]. As a key component of the cohesin complex, it is involved in sister chromatid cohesion, which is crucial for proper chromosome segregation, post-replicative DNA repair, and preventing inappropriate recombination. In interphase, it also controls gene expression by binding to numerous genomic sites. Additionally, RAD21 is linked to apoptotic pathways [2].

In ovarian cancer, RAD21 amplification epigenetically suppresses interferon signaling to promote immune evasion. RAD21 directly interacts with YAP/TEAD4 transcriptional corepressors and recruits the NuRD complex to suppress IFN signaling, and its overexpression is inversely correlated with IFN signature gene expression. RAD21 ablation in murine syngeneic tumor models potentiated anti-PD-1 efficacy with increased intratumoral CD8+ T cell effector activity [1]. In prostate cancer, increased RAD21 alleviated toxic oncogenic stress and DNA damage caused by oncogene expression, enabling aggressive tumors to sustain proliferation [3]. In acute myeloid leukemia, RAD21-mutated cases often associate with monocytic differentiation, CD7 expression, co-existing mutations in epigenetic regulators, a normal karyotype, and poor prognosis [4].

In conclusion, RAD21 plays essential roles in processes like chromosome segregation, DNA repair, and gene expression regulation. Model-based research, such as in murine syngeneic tumor models for ovarian cancer, has revealed its significant implications in cancer development and progression, including immune evasion in ovarian cancer, lethal progression in prostate cancer, and poor prognosis in acute myeloid leukemia.