SIKE1, also known as suppressor of IKBKE 1, is involved in multiple biological processes. It is part of the striatin-interacting phosphatase and kinase (STRIPAK) complex in the Hippo signaling pathway. In response to genotoxic stress, it participates in relaying nuclear DNA damage signals through the cGAS/STING pathway [1,2]. SIKE1 is also associated with immune-related processes in chickens, as it is a core gene in corticosterone-induced stress and dexamethasone-induced immunosuppression models [3,4].

In rodents and non-human primates, Sike-deficient mice develop cardiac hypertrophy and heart failure, suggesting that SIKE1 is a negative regulator of pathological cardiac hypertrophy, likely through its interaction with TBK1 to inhibit the TBK1-AKT signaling pathway [5]. In human mesenchymal stem cells, SIKE1 is a direct target of miR-146a-5p, and knockdown of miR-146a-5p affects the activity of NF-κB, which is related to cell proliferation and migration [6].

In conclusion, SIKE1 plays essential roles in the Hippo signaling pathway, DNA damage response, immune-related processes in chickens, and as a negative regulator of pathological cardiac hypertrophy. The gene knockout models in rodents have revealed its importance in cardiac disease, highlighting its potential as a therapeutic target for heart-related conditions.

References:

1. An, Liwei, Cao, Zhifa, Nie, Pingping, Jiao, Shi, Zhou, Zhaocai. . Combinatorial targeting of Hippo-STRIPAK and PARP elicits synthetic lethality in gastrointestinal cancers. In The Journal of clinical investigation, 132, . doi:10.1172/JCI155468. https://pubmed.ncbi.nlm.nih.gov/35290241/

2. Tang, Yang, Chen, Min, Zhou, Li, Jiao, Shi, Zhou, Zhaocai. 2019. Architecture, substructures, and dynamic assembly of STRIPAK complexes in Hippo signaling. In Cell discovery, 5, 3. doi:10.1038/s41421-018-0077-3. https://pubmed.ncbi.nlm.nih.gov/30622739/

3. Su, Aru, Zhou, Yanting, Guo, Yujie, Kang, Xiangtao, Yan, Fengbin. 2021. Identification and expression analysis of MicroRNAs in chicken spleen in a corticosterone-induced stress model. In Research in veterinary science, 136, 287-296. doi:10.1016/j.rvsc.2021.02.023. https://pubmed.ncbi.nlm.nih.gov/33740563/

4. Su, Aru, Guo, Yujie, Tian, Huihui, Yan, Fengbin, Kang, Xiangtao. 2021. Analysis of miRNA and mRNA reveals core interaction networks and pathways of dexamethasone-induced immunosuppression in chicken bursa of Fabricius. In Molecular immunology, 134, 34-47. doi:10.1016/j.molimm.2021.02.022. https://pubmed.ncbi.nlm.nih.gov/33711668/

5. Deng, Ke-Qiong, Wang, Aibing, Ji, Yan-Xiao, Pu, Jun, Li, Hongliang. 2016. Suppressor of IKKɛ is an essential negative regulator of pathological cardiac hypertrophy. In Nature communications, 7, 11432. doi:10.1038/ncomms11432. https://pubmed.ncbi.nlm.nih.gov/27249321/

6. Hsieh, Jui-Yu, Huang, Tse-Shun, Cheng, Shu-Meng, Lee, Oscar K, Wang, Hsei-Wei. 2013. miR-146a-5p circuitry uncouples cell proliferation and migration, but not differentiation, in human mesenchymal stem cells. In Nucleic acids research, 41, 9753-63. doi:10.1093/nar/gkt666. https://pubmed.ncbi.nlm.nih.gov/23963696/