Scn4b, encoding voltage-gated sodium channel β subunit 4, is crucial for modulating neuronal activity by regulating channel gating [2]. It is also involved in cell adhesion and migration processes. The voltage-gated sodium channels, of which Scn4b is a part, are responsible for action potential generation and are associated with various biological functions in excitable tissues [4].

Genetic global knockout (KO) of Scn4b in mice showed that while it did not affect ethanol consumption, it was involved in the acute hypnotic effects of ethanol and other sedatives like gaboxadol, pentobarbital, and ketamine [2]. In cancer research, Scn4b has been studied in multiple types of cancer. In lung adenocarcinoma (LUAD), it was found to be expressed higher in normal samples than in cancer samples, and higher expression was associated with better prognosis. It may be regulated by transcription factors TAL1 and ERG [1]. In non-small cell lung cancer (NSCLC), low expression of Scn4b was associated with poor prognosis, and it was involved in NSCLC-related KEGG pathways and immune infiltration [3]. In papillary thyroid cancer (PTC), preserved Scn4b expression was an independent indicator of favorable recurrence-free survival, and its expression might be suppressed by DNA hypermethylation [5]. In breast cancer, reduced β4 (encoded by Scn4b) protein levels correlated with high-grade primary and metastatic tumours, and Scn4b overexpression reduced cancer cell invasiveness, indicating it as a metastasis-suppressor gene [6].

In conclusion, Scn4b plays important roles in neuronal function related to the hypnotic effects of certain drugs. In cancer, it has potential as a prognostic biomarker and is involved in metastasis regulation in multiple cancer types. The study of Scn4b using gene knockout mouse models has provided valuable insights into its functions in these biological processes and disease conditions [1,2,3,5,6].

References:

1. Ma, Minting, Guo, Bin, Lu, Hongwei, Hong, Lei. 2023. SCN4B inhibits the progression of lung adenocarcinoma and is associated with better prognosis. In The clinical respiratory journal, 17, 1233-1245. doi:10.1111/crj.13709. https://pubmed.ncbi.nlm.nih.gov/37826914/

2. Blednov, Yuri A, Bajo, Michal, Roberts, Amanda J, Hitzemann, Robert J, Harris, Robert A. 2019. Scn4b regulates the hypnotic effects of ethanol and other sedative drugs. In Genes, brain, and behavior, 18, e12562. doi:10.1111/gbb.12562. https://pubmed.ncbi.nlm.nih.gov/30817077/

3. Li, Xia, Chen, Weiwei, Jiang, Shu, Ni, Qinggan, Ling, Chunhua. . Low Expression of SCN4B Predicts Poor Prognosis in Non-small Cell Lung Cancer. In Current cancer drug targets, 25, 445-466. doi:10.2174/0115680096293516240607071915. https://pubmed.ncbi.nlm.nih.gov/38956906/

4. Pan, Xiaojing, Li, Zhangqiang, Zhou, Qiang, Xiao, Bailong, Yan, Nieng. 2018. Structure of the human voltage-gated sodium channel Nav1.4 in complex with β1. In Science (New York, N.Y.), 362, . doi:10.1126/science.aau2486. https://pubmed.ncbi.nlm.nih.gov/30190309/

5. Gong, Yanping, Yang, Jing, Wu, Wenshuang, Zhu, Jingqiang, Wei, Tao. 2018. Preserved SCN4B expression is an independent indicator of favorable recurrence-free survival in classical papillary thyroid cancer. In PloS one, 13, e0197007. doi:10.1371/journal.pone.0197007. https://pubmed.ncbi.nlm.nih.gov/29723302/

6. Bon, Emeline, Driffort, Virginie, Gradek, Frédéric, Besson, Pierre, Roger, Sébastien. 2016. SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer. In Nature communications, 7, 13648. doi:10.1038/ncomms13648. https://pubmed.ncbi.nlm.nih.gov/27917859/