Kpna2, also known as karyopherin α2 or importinα-1, is a member of the nuclear transport protein family. It is involved in the nucleocytoplasmic transport pathway of various proteins, participating in multiple cellular activities such as cell differentiation, proliferation, apoptosis, and immune response [2]. It has been associated with pathways like STAT3 phosphorylation, which is relevant in angiogenesis [1].

In a murine hindlimb ischemia model, overexpression of Kpna2 promoted angiogenesis as it increased HUVEC proliferation, migration, and tube formation under hypoxia, while knockout of Kpna2 inhibited these processes. Mechanistically, hypoxia promoted the binding of STAT3 to Kpna2, and Kpna2 regulated STAT3 phosphorylation to up-or down-regulate angiogenesis-related factors like VEGF and ANGPT2 [1]. In renal cell carcinoma, knockdown of Kpna2 in vitro inhibited cell proliferation and invasion, induced cell cycle arrest and apoptosis, and in nude mice, it repressed tumorigenesis and development. It was also found that Kpna2 may regulate NPM to play a crucial role in kidney tumour development [3]. In osteosarcoma, removal of Kpna2 significantly suppressed cell growth, migration, and invasion in vitro and tumor growth in vivo [4]. In an atherosclerotic mouse model, knockdown of Kpna2 in HUVECs inhibited the secretion of pro-inflammatory factors and monocyte-endothelial adhesion, and in vivo, it alleviated endothelial dysfunction and related inflammation by blocking the nuclear translocation of p65 and IRF3 [5].

In conclusion, Kpna2 plays essential roles in angiogenesis, tumorigenesis, and inflammation-related processes. Gene knockout or knockdown models in mice and cell lines have revealed its functions in promoting angiogenesis, cancer cell proliferation, and metastasis, as well as its pro-inflammatory role in atherosclerosis. These findings highlight its potential as a therapeutic target in related diseases.

References:

1. Jia, Yujie, Wang, Qi, Liang, Minglu, Huang, Kai. 2022. KPNA2 promotes angiogenesis by regulating STAT3 phosphorylation. In Journal of translational medicine, 20, 627. doi:10.1186/s12967-022-03841-6. https://pubmed.ncbi.nlm.nih.gov/36578083/

2. Han, Yang, Wang, Xin. 2019. The emerging roles of KPNA2 in cancer. In Life sciences, 241, 117140. doi:10.1016/j.lfs.2019.117140. https://pubmed.ncbi.nlm.nih.gov/31812670/

3. Zheng, Song, Li, Xiaofan, Deng, Ting, Guo, Yinan, Chen, Jianhui. 2021. KPNA2 promotes renal cell carcinoma proliferation and metastasis via NPM. In Journal of cellular and molecular medicine, 25, 9255-9267. doi:10.1111/jcmm.16846. https://pubmed.ncbi.nlm.nih.gov/34469024/

4. Xia, Shuchi, Ma, Yiqun. 2022. IRF2 Destabilizes Oncogenic KPNA2 to Modulate the Development of Osteosarcoma. In Journal of oncology, 2022, 9973519. doi:10.1155/2022/9973519. https://pubmed.ncbi.nlm.nih.gov/36199790/

5. Xing, Zeyu, Zhen, Yanhua, Chen, Jie, Liu, Ruyin, Zheng, Jiahe. 2023. KPNA2 Silencing, Regulated by E3 Ubiquitin Ligase FBXW7, Alleviates Endothelial Dysfunction and Inflammation Through Inhibiting the Nuclear Translocation of p65 and IRF3: A Possible Therapeutic Approach for Atherosclerosis. In Inflammation, 46, 2071-2088. doi:10.1007/s10753-023-01863-w. https://pubmed.ncbi.nlm.nih.gov/37432596/