Prkdc, which encodes the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), is crucial for nonhomologous end-joining DNA repair. This process is essential for maintaining genomic stability, as it repairs double-strand breaks in DNA. It has been associated with various biological processes and diseases, highlighting its overall biological importance. Genetic models, such as KO/CKO mouse models, are valuable tools for studying Prkdc's functions [3].

In osteosarcoma, loss-of-function experiments showed that the loss of Prkdc significantly increased sensitivity to doxorubicin. Mechanistically, Prkdc recruits and binds GDE2 to enhance the stability of GNAS protein, which activates AKT phosphorylation and confers resistance to doxorubicin [1].

In gastric cancer, hsa_circ_0136666 upregulates Prkdc expression by sponging miR-375-3p, regulating immune checkpoint proteins, prompting PD-L1 phosphorylation, and driving immune escape [2].

In skin wound healing, knockdown of circ_PRKDC promoted keratinocyte migration through the miR-31/FBN1 axis [4].

In liver hepatocellular carcinoma, targeting Prkdc activates antitumor immunity and sensitizes to chemotherapy and targeted therapy [5].

In conclusion, Prkdc plays a key role in DNA repair and is involved in multiple disease processes. Model-based research, especially KO/CKO mouse models, has revealed its functions in osteosarcoma chemoresistance, gastric cancer immune escape, skin wound healing, and liver cancer treatment response, providing potential therapeutic targets for these diseases.