NCAPD2, also known as Non-SMC condensin I complex subunit D2, is one of the three non-SMC subunits in condensin I. It plays a crucial role in chromosome condensation and segregation. It is involved in multiple pathways such as Ca2+/CAMKK2/AMPK/mTORC1, PARP-1/SIRT1, PI3K‑Akt‑mTOR, and Wnt/β-catenin, which are relevant to various biological processes and disease development [1,2,3,5]. Gene knockout (KO) and conditional knockout (CKO) mouse models are valuable for studying its function.

In KO mouse models, NCAPD2 knockout suppresses colorectal cancer development in an AOM/DSS induced mice model, indicating its role as a tumor promoter in CRC through inhibiting autophagy via Ca2+/CAMKK2/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis [1]. In a TNBS-induced CD mouse model, NCAPD2 knockdown inhibited the development of TNBS-induced intestinal inflammation, suggesting that NCAPD2 promotes Crohn's disease progression by suppressing autophagy and activating the NF-κB signaling pathway [4].

In conclusion, NCAPD2 is essential for chromosome-related functions and is involved in multiple disease-related pathways. The KO/CKO mouse models have revealed its role in promoting the development of diseases like colorectal cancer and Crohn's disease, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Jing, Zuolei, He, Xinyuan, Jia, Zhirong, Yang, Bolin, Liu, Ping. 2021. NCAPD2 inhibits autophagy by regulating Ca2+/CAMKK2/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis to promote colorectal cancer. In Cancer letters, 520, 26-37. doi:10.1016/j.canlet.2021.06.029. https://pubmed.ncbi.nlm.nih.gov/34229059/

2. Gu, Jiang-Xue, Huang, Ke, Zhao, Wei-Lin, Huang, Yu-Gang, Hu, Pei. 2024. NCAPD2 augments the tumorigenesis and progression of human liver cancer via the PI3K‑Akt‑mTOR signaling pathway. In International journal of molecular medicine, 54, . doi:10.3892/ijmm.2024.5408. https://pubmed.ncbi.nlm.nih.gov/39092569/

3. Ma, Ping, Yu, Huajiao, Zhu, Mingda, Han, Zhengxue, Jin, Wulong. 2024. NCAPD2 promotes the malignant progression of oral squamous cell carcinoma via the Wnt/β-catenin pathway. In Cell cycle (Georgetown, Tex.), 23, 588-601. doi:10.1080/15384101.2024.2348918. https://pubmed.ncbi.nlm.nih.gov/38743408/

4. Ge, Hao, Wang, Can, Zhao, Haoran, Liu, Ping, Yang, Bolin. . Targeting NCAPD2 as a Therapeutic Strategy for Crohn's Disease: Implications for Autophagy and Inflammation. In Inflammatory bowel diseases, 31, 178-188. doi:10.1093/ibd/izae211. https://pubmed.ncbi.nlm.nih.gov/39340820/

5. Mai, Yuhua, Liao, Chuanjie, Wang, Shengyu, Qin, Yingfen, Deng, Ganlu. 2024. High glucose-induced NCAPD2 upregulation promotes malignant phenotypes and regulates EMT via the Wnt/β-catenin signaling pathway in HCC. In American journal of cancer research, 14, 1685-1711. doi:10.62347/HYNZ9211. https://pubmed.ncbi.nlm.nih.gov/38726276/