Kcnj14, encoding the inwardly rectifying potassium channel Kir2.4, is involved in regulating membrane potential and ion homeostasis. It is associated with multiple biological processes, such as the regulation of resting potentials and excitability in colonic muscles where it may contribute to the Ba²⁺ -sensitive, inwardly rectifying K⁺ conductance likely through the formation of heterotetramers with other Kir2 gene products [3]. It has also been linked to various pathways including mTOR, NOD-like receptor, and VEGF signalling pathways [1].

In colorectal cancer, Kcnj14 expression is increased in tissues and cell lines, reducing patient overall survival time. Knockdown of Kcnj14 significantly inhibits the proliferation and migration of colorectal cancer cell lines and decreases the levels of mTOR signalling pathway-related proteins [1]. In a broader cancer context, Kcnj14 is dysregulated in multiple cancer types like lung, intestinal, head and neck, oesophageal, and stomach cancers. It is associated with RNA and DNA stemness, immunological checkpoints, suppressor cells, tumour mutation burden, microsatellite instability, neoantigen, and programmed death ligand 1, suggesting it may be a useful independent prognostic biomarker for a range of cancers [2].

In summary, Kcnj14 plays a significant role in maintaining ion-related physiological functions. Its dysregulation is linked to colorectal and other cancers, and studies on Kcnj14, potentially through gene-knockout models in the future, may provide valuable insights into cancer mechanisms and offer new therapeutic targets for cancer treatment [1,2].

References:

1. Li, Bin, Ge, Ning, Pan, Zhongping, Li, Mengyi, Luo, Shuping. 2022. KCNJ14 knockdown significantly inhibited the proliferation and migration of colorectal cells. In BMC medical genomics, 15, 194. doi:10.1186/s12920-022-01351-4. https://pubmed.ncbi.nlm.nih.gov/36100894/

2. Alasiri, Glowi. 2023. Comprehensive Analysis of KCNJ14 Potassium Channel as a Biomarker for Cancer Progression and Development. In International journal of molecular sciences, 24, . doi:10.3390/ijms24032049. https://pubmed.ncbi.nlm.nih.gov/36768373/

3. 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/