Prkdc, also known as Protein Kinase, DNA-Activated, Catalytic Polypeptide, encodes the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). DNA-PKcs plays a major role in nonhomologous end-joining DNA repair, which is crucial for maintaining genomic stability. It has been implicated in various biological processes and is associated with pathways like cell cycle regulation. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions [3].

In osteosarcoma, loss-of-function experiments showed that the loss of Prkdc significantly increased sensitivity to doxorubicin, as Prkdc recruited GDE2 to stabilize GNAS and activate AKT, conferring chemoresistance [1]. In gastric cancer, hsa_circ_0136666 upregulated Prkdc expression by sponging miR-375-3p, promoting tumor progression and immune escape [2]. In skin wound healing, knockdown of circ_PRKDC promoted keratinocyte migration through the miR-31/FBN1 axis [4]. In pan-cancer analysis, high Prkdc expression was associated with a worse prognosis, while its mutations might lead to better survival [5]. In ovarian cancer, PRKDC-mediated non-homologous end-joining may play a crucial role in chromosome 8 aneuploidy-driven progression [6]. In liver hepatocellular carcinoma, targeting Prkdc activated antitumor immunity and sensitized to chemotherapy and targeted therapy [7]. In renal transplantation, up-regulation of Prkdc in the donor kidney was associated with poor renal dysfunction after transplantation [8].

In conclusion, Prkdc is essential for DNA repair and has far-reaching impacts on multiple biological processes. Studies using KO/CKO mouse models and other loss-of-function experiments have revealed its roles in various disease conditions, including cancer and post-transplantation renal dysfunction. Understanding Prkdc functions provides potential therapeutic targets for these diseases.

References:

1. Zhang, Wenchao, Li, Wei, Yin, Chi, Tu, Chao, Li, Zhihong. . PRKDC Induces Chemoresistance in Osteosarcoma by Recruiting GDE2 to Stabilize GNAS and Activate AKT. In Cancer research, 84, 2873-2887. doi:10.1158/0008-5472.CAN-24-0163. https://pubmed.ncbi.nlm.nih.gov/38900943/

2. Miao, Zhenyan, Li, Jifei, Wang, Yu, Zheng, Lufeng, Xing, Yingying. 2023. Hsa_circ_0136666 stimulates gastric cancer progression and tumor immune escape by regulating the miR-375/PRKDC Axis and PD-L1 phosphorylation. In Molecular cancer, 22, 205. doi:10.1186/s12943-023-01883-y. https://pubmed.ncbi.nlm.nih.gov/38093288/

3. Yin, Yuting, He, Qinglian, Li, Yuling, Li, Ziqi, Zhu, Wei. 2020. Emerging functions of PRKDC in the initiation and progression of cancer. In Tumori, 107, 483-488. doi:10.1177/0300891620950472. https://pubmed.ncbi.nlm.nih.gov/32867618/

4. Han, Dawei, Liu, Wenhui, Li, Guangshuai, Liu, Linbo. 2021. Circ_PRKDC knockdown promotes skin wound healing by enhancing keratinocyte migration via miR-31/FBN1 axis. In Journal of molecular histology, 52, 681-691. doi:10.1007/s10735-021-09996-8. https://pubmed.ncbi.nlm.nih.gov/34143322/

5. Yang, Xiawei, Yang, Feng, Lan, Liugen, Li, Haibin, Sun, Xuyong. 2022. Potential value of PRKDC as a therapeutic target and prognostic biomarker in pan-cancer. In Medicine, 101, e29628. doi:10.1097/MD.0000000000029628. https://pubmed.ncbi.nlm.nih.gov/35801800/

6. Luan, Wenqing, Cheng, Hongyan, Xie, Haoling, Li, Yi, Chang, Xiaohong. 2024. PRKDC-Mediated NHEJ May Play a Crucial Role in Aneuploidy of Chromosome 8-Driven Progression of Ovarian Cancer. In International journal of molecular sciences, 25, . doi:10.3390/ijms25094825. https://pubmed.ncbi.nlm.nih.gov/38732044/

7. Pan, Yitong, Zhu, Qiyao, Hong, Ting, Cheng, Jun, Tang, Xinhui. 2024. Targeting PRKDC activates the efficacy of antitumor immunity while sensitizing to chemotherapy and targeted therapy in liver hepatocellular carcinoma. In Aging, 16, 9047-9071. doi:10.18632/aging.205855. https://pubmed.ncbi.nlm.nih.gov/38787389/

8. Cao, Zhijun, Jiang, Hao, Zhao, Chunchun, Jiang, Minjun, Wang, Zhenfan. 2023. Up-regulation of PRKDC was associated with poor renal dysfunction after renal transplantation: A multi-centre analysis. In Journal of cellular and molecular medicine, 27, 1362-1372. doi:10.1111/jcmm.17737. https://pubmed.ncbi.nlm.nih.gov/37002788/