Ubn2-KO Mouse

Ubn2, also known as ubinuclein-2, is a nuclear protein that interacts with many transcription factors. It is a subunit of the HIRA complex, which is responsible for the recognition and deposition of H3.3 histone variant at cis-regulatory elements of genes, playing a role in transcriptional regulation [7]. It is also involved in pathways related to tumor progression and cell fate determination [1,6].

In colorectal cancer, knockdown of Ubn2 inhibited the growth, invasiveness and metastasis of CRC cells via regulation of the Ras/MAPK signaling pathway, indicating that Ubn2 promotes tumor progression and can be a biomarker for predicting prognosis [1]. In prostate cancer, Ubn2 was identified as a downstream target gene of ADAM9, and it is critical for the survival of androgen-dependent PCa cells in response to androgen deprivation through the induction of AKR1C3, contributing to androgen-deprivation therapy resistance [2]. In acute myeloid leukemia, miR-455-3p mediates PPARα through Ubn2, exacerbating AML cell apoptosis and autophagy [3]. In non-small-cell lung cancer, circ_0060967 facilitates NSCLC progression by enhancing UBN2 expression via sponging miR-660-3p [4]. In colorectal cancer, miR-802 inhibits the proliferation, migration and invasion while promotes the apoptosis of CRC cells via directly suppressing UBN2 expression [5]. In embryonic stem cells, Ubn2 is one of the main repressors of 2-cell marker retrotransposon MERVL among HIRA complex members, and it prevents ESCs from gaining a 2-cell like state or activating trophectodermal genes upon differentiation [6].

In conclusion, Ubn2 is involved in multiple biological processes, especially in tumor-related pathways such as Ras/MAPK. Gene-knockout or knockdown models in different cell lines and in vivo mouse models have been crucial in revealing its role in cancer development, cell fate determination, and apoptosis/autophagy regulation, providing potential targets for cancer treatment.

References:

1. Zhao, Ya-Li, Zhong, Shen-Rong, Zhang, Shi-Hong, Liang, Li, Liao, Wen-Ting. 2019. UBN2 promotes tumor progression via the Ras/MAPK pathway and predicts poor prognosis in colorectal cancer. In Cancer cell international, 19, 126. doi:10.1186/s12935-019-0848-4. https://pubmed.ncbi.nlm.nih.gov/31110467/

2. Le, Trang Thi-Huynh, Hsieh, Chia-Ling, Lin, I-Hsuan, Chen, Kuan-Chou, Sung, Shian-Ying. 2022. The ADAM9/UBN2/AKR1C3 axis promotes resistance to androgen-deprivation in prostate cancer. In American journal of cancer research, 12, 176-197. doi:. https://pubmed.ncbi.nlm.nih.gov/35141012/

3. Xie, Yu, Tan, Lin, Wu, Kun, Li, Deyun, Li, Chengping. 2023. MiR-455-3p mediates PPARα through UBN2 to promote apoptosis and autophagy in acute myeloid leukemia cells. In Experimental hematology, 128, 77-88. doi:10.1016/j.exphem.2023.09.007. https://pubmed.ncbi.nlm.nih.gov/37805161/

4. Zhu, Zheng, Zhang, Ke, Lou, Ming, Lu, Jiawei, Yuan, Kai. 2022. Circ_0060967 facilitates proliferation, migration, and invasion of non-small-cell lung cancer cells by sponging miR-660-3p/UBN2. In Molecular and cellular biochemistry, 478, 1129-1140. doi:10.1007/s11010-022-04569-z. https://pubmed.ncbi.nlm.nih.gov/36229758/

5. Yang, Tao, Guo, Qiuying, Li, Dongsheng, Sun, Hongzhi, Wang, Wei. 2020. MicroRNA-802 Suppresses Tumorigenesis of Colorectal Cancer via Regulating UBN2. In Cancer management and research, 12, 11219-11230. doi:10.2147/CMAR.S267345. https://pubmed.ncbi.nlm.nih.gov/33177873/

6. Zhang, Miao, Zhao, Xin, Feng, Xiao, Lu, Wange, Lu, Xinyi. 2022. Histone chaperone HIRA complex regulates retrotransposons in embryonic stem cells. In Stem cell research & therapy, 13, 137. doi:10.1186/s13287-022-02814-2. https://pubmed.ncbi.nlm.nih.gov/35365225/

7. Xiong, Chaoyang, Wen, Zengqi, Yu, Juan, Xu, Rui-Ming, Li, Guohong. 2018. UBN1/2 of HIRA complex is responsible for recognition and deposition of H3.3 at cis-regulatory elements of genes in mouse ES cells. In BMC biology, 16, 110. doi:10.1186/s12915-018-0573-9. https://pubmed.ncbi.nlm.nih.gov/30285846/