NCAPD3, a subunit of the non-SMC condensin II complex, is mainly responsible for chromosome condensation and segregation during mitosis [1,2,3,4,5]. It has been implicated in various cellular processes and is associated with multiple signaling pathways, though its specific molecular connections are still being explored. Genetic models, such as gene knockout mouse models, have been valuable in elucidating its functions.

In multiple cancers, NCAPD3 shows oncogenic properties. In colorectal cancer, NCAPD3 knockout suppressed tumor development in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced and xenograft mouse models. It promoted aerobic glycolysis by up-regulating c-Myc and E2F1, which in turn regulated downstream glycolytic genes [1]. In prostate cancer, knockdown of NCAPD3 impaired cell growth, while overexpression enhanced it. NCAPD3 up-regulated EZH2 and MALAT1 through STAT3 and E2F1 [2]. In diffuse large B-cell lymphoma, NCAPD3 deficiency impeded cell proliferation, induced apoptosis, and increased chemosensitivity, and in vivo experiments showed that targeting NCAPD3 suppressed tumor growth [3]. In non-small cell lung cancer, knockdown of NCAPD3 led to cell apoptosis, cell cycle arrest, and inhibited proliferation, invasion, and migration, and RNA-sequencing suggested it regulated the PI3K/Akt/FOXO4 pathway [6].

In conclusion, NCAPD3 is crucial for chromosome-related functions during mitosis. Model-based research, especially gene knockout mouse models, has revealed its significant role in promoting tumorigenesis in multiple cancer types, including colorectal, prostate, lymphoma, and non-small cell lung cancers. Understanding NCAPD3 provides potential therapeutic targets for these diseases.

References:

1. Jing, Zuolei, Liu, Qianmei, He, Xinyuan, Yang, Bolin, Liu, Ping. 2022. NCAPD3 enhances Warburg effect through c-myc and E2F1 and promotes the occurrence and progression of colorectal cancer. In Journal of experimental & clinical cancer research : CR, 41, 198. doi:10.1186/s13046-022-02412-3. https://pubmed.ncbi.nlm.nih.gov/35689245/

2. Jing, Zuolei, Liu, Qianmei, Xie, Wanlin, Zhu, Qingyi, Liu, Ping. 2022. NCAPD3 promotes prostate cancer progression by up-regulating EZH2 and MALAT1 through STAT3 and E2F1. In Cellular signalling, 92, 110265. doi:10.1016/j.cellsig.2022.110265. https://pubmed.ncbi.nlm.nih.gov/35085770/

3. Lu, Tiange, Yang, Juan, Cai, Yiqing, Zhou, Xiangxiang, Wang, Xin. 2024. NCAPD3 promotes diffuse large B-cell lymphoma progression through modulating SIRT1 expression in an H3K9 monomethylation-dependent manner. In Journal of advanced research, 68, 163-178. doi:10.1016/j.jare.2024.02.024. https://pubmed.ncbi.nlm.nih.gov/38432395/

4. Zhang, Yi, Shao, Yingying, Ren, Jia, Lu, Shan, Liu, Ping. 2024. NCAPD3 exerts tumor-promoting effects in prostatic cancer via dual impact on miR-30a-5p by STAT3-MALAT1 and MYC. In Cell death discovery, 10, 159. doi:10.1038/s41420-024-01930-7. https://pubmed.ncbi.nlm.nih.gov/38561330/

5. Yin, Yingying, Liu, Qianmei, Shao, Yingying, Lu, Shan, Liu, Ping. 2021. Regulatory mechanism of androgen receptor on NCAPD3 gene expression in prostate cancer. In The Prostate, 82, 26-40. doi:10.1002/pros.24245. https://pubmed.ncbi.nlm.nih.gov/34591337/

6. Yang, Fan, Zheng, Yunfeng, Luo, Qiong, Yang, Sheng, Chen, Xiangqi. 2024. Knockdown of NCAPD3 inhibits the tumorigenesis of non-small cell lung cancer by regulation of the PI3K/Akt pathway. In BMC cancer, 24, 408. doi:10.1186/s12885-024-12131-x. https://pubmed.ncbi.nlm.nih.gov/38566039/