Sesn1, also known as PA26, is a stress-inducible protein with multiple essential functions. It is involved in various biological pathways, such as those related to muscle aging, tumor suppression, innate immune homeostasis, and more. Its role in these pathways makes it biologically significant in understanding normal physiological processes and disease development. Genetic models, like gene knockout models, have been crucial in studying Sesn1's functions [1-10].

In a zebrafish sesn1-knockdown model, Sesn1 was shown to be required for normal embryonic left-right determination and to play a role in mediating Nodal signaling [4]. In mice, lacking Sesn1 and Sesn2 led to an inability to inhibit mTORC1 upon dietary leucine deprivation, resulting in rapid loss of white adipose tissue and muscle [5]. In human-related studies, knockdown of Sesn1 in human myotubes mimicked aging phenotypes, while its genetic activation alleviated senescence, indicating its role in counteracting human skeletal muscle aging [1]. In neuroblastoma cells, knockdown of Sesn1 promoted cell proliferation, migration, and invasion, and shortened tumor-bearing mice survival time, suggesting it functions as a tumor suppressor [2]. Also, in HNSCC, low Sesn1 expression was correlated with poor prognosis, and its overexpression inhibited cell proliferation, migration, and invasion [3].

In conclusion, Sesn1 plays diverse and essential biological functions. Through model-based research, it has been revealed to be involved in muscle aging, tumor development, left-right asymmetry determination, and response to dietary leucine. The use of gene-knockdown or knockout models in different organisms has significantly contributed to understanding its role in these specific disease areas and biological processes, providing potential diagnostic biomarkers and intervention strategies for related diseases [1-10].

References:

1. Jing, Ying, Zuo, Yuesheng, Sun, Liang, Liu, Guang-Hui, Wang, Si. 2023. SESN1 is a FOXO3 effector that counteracts human skeletal muscle ageing. In Cell proliferation, 56, e13455. doi:10.1111/cpr.13455. https://pubmed.ncbi.nlm.nih.gov/37199024/

2. Hua, Zhongyan, Chen, Bo, Gong, Baocheng, Ma, Yifan, Li, Zhijie. . SESN1 functions as a new tumor suppressor gene via Toll-like receptor signaling pathway in neuroblastoma. In CNS neuroscience & therapeutics, 30, e14664. doi:10.1111/cns.14664. https://pubmed.ncbi.nlm.nih.gov/38516781/

3. Zhang, Chi, Ren, Lin, Zhang, Hongjian, Zhao, Chuanjiang, Xia, Juan. 2022. SESN1, negatively regulated by miR-377-3p, suppresses invasive growth of head and neck squamous cell carcinoma by interaction with SMAD3. In Human cell, 35, 1100-1113. doi:10.1007/s13577-022-00719-z. https://pubmed.ncbi.nlm.nih.gov/35622213/

4. Peeters, Hilde, Voz, Marianne L, Verschueren, Kristin, Peers, Bernard, Devriendt, Koen. 2006. Sesn1 is a novel gene for left-right asymmetry and mediating nodal signaling. In Human molecular genetics, 15, 3369-77. doi:. https://pubmed.ncbi.nlm.nih.gov/17038485/

5. Cangelosi, Andrew L, Puszynska, Anna M, Roberts, Justin M, Helman, Aharon, Sabatini, David M. 2022. Zonated leucine sensing by Sestrin-mTORC1 in the liver controls the response to dietary leucine. In Science (New York, N.Y.), 377, 47-56. doi:10.1126/science.abi9547. https://pubmed.ncbi.nlm.nih.gov/35771919/