Kcnj4, also known as potassium voltage-gated channel subfamily J member 4, belongs to the inward rectifier potassium channel family. It is involved in regulating membrane potential and excitability in various tissues. In the gastrointestinal tract, it contributes to the regulation of resting potentials and excitability of colonic muscles, potentially through forming heterotetramers with other Kir2 gene products [4]. In the brain, it may be related to synaptic function as indicated by its presence in a list of candidate genes for schizophrenia [5].

In lung adenocarcinoma (LADC), siRNA-mediated Kcnj4 silencing impeded cell proliferation, migration, and invasion. Knockdown of Kcnj4 also suppressed the expression of phosphorylated mitogen-activated protein kinase/extracellular signal regulated kinase (p-MEK) and phosphorylated extracellular signal-regulated kinase (p-ERK), suggesting its role in LADC progression [1]. Additionally, in LADC, lncRNA POU6F2-AS1 may act as a competing endogenous RNA (ceRNA) of miR-34c-5p to facilitate Kcnj4 expression, influencing LADC cell aggressiveness [2]. In the context of manganese-induced neurotoxicity, vitamin E's neuroprotective effects may be related to the up-regulation of Kcnj4 mRNA in the substantia nigra [3].

In summary, Kcnj4 plays essential roles in maintaining normal physiological functions in multiple tissues. Its dysregulation is associated with diseases like lung adenocarcinoma and may be involved in neuroprotective mechanisms. Functional studies, such as those using siRNA-mediated silencing in LADC cells, have provided insights into its role in disease-related biological processes.

References:

1. Wu, Xiao-Yan, Yu, Xue-Yan. 2018. Overexpression of KCNJ4 correlates with cancer progression and unfavorable prognosis in lung adenocarcinoma. In Journal of biochemical and molecular toxicology, 33, e22270. doi:10.1002/jbt.22270. https://pubmed.ncbi.nlm.nih.gov/30512237/

2. Wu, Xiao-Yan, Xie, Yi, Zhou, Li-Yun, Guo, Shuai, Yu, Xue-Yan. 2021. Long noncoding RNA POU6F2-AS1 regulates lung cancer aggressiveness through sponging miR-34c-5p to modulate KCNJ4 expression. In Genetics and molecular biology, 44, e20200050. doi:10.1590/1678-4685-GMB-2020-0050. https://pubmed.ncbi.nlm.nih.gov/33999092/

3. Song, Ruihan, Chen, Huanhuan, Zhan, Runqing, Zhao, Longzhu, Shen, Xiaoli. 2023. Vitamin E protects dopaminergic neurons against manganese-induced neurotoxicity through stimulation of CHRM1 and KCNJ4. In Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 81, 127326. doi:10.1016/j.jtemb.2023.127326. https://pubmed.ncbi.nlm.nih.gov/37939525/

4. Huang, Xu, Lee, Si Hyung, Lu, Hongli, Sanders, Kenton M, Koh, Sang Don. 2017. Molecular and functional characterization of inwardly rectifying K+ currents in murine proximal colon. In The Journal of physiology, 596, 379-391. doi:10.1113/JP275234. https://pubmed.ncbi.nlm.nih.gov/29205356/

5. Le-Niculescu, H, Balaraman, Y, Patel, S, Tsuang, M T, Niculescu, A B. . Towards understanding the schizophrenia code: an expanded convergent functional genomics approach. In American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 144B, 129-58. doi:. https://pubmed.ncbi.nlm.nih.gov/17266109/