Transcriptomic analysis of U-373MG exposed to synthetic ShK-like peptide from the Jellyfish

Jellyfish-derived ShK-like peptides are potent blockers of the voltage-gated potassium channel Kv1.3, which plays key roles in immune cell activation and glioblastoma cell physiology. In this study, we investigated the transcriptomic responses of U-373MG human glioblastoma cells exposed to two synthetic ShK-like peptides, NnK-1 (derived from Nemopilema nomurai) and CBRV1-10493 (derived from Carybdea brevipedalia), at 200 nM for 48 h (n = 3 per group). Since neither peptide affected cell viability at this concentration, 200 nM was selected as the treatment dose. Gene expression profiling was performed using QuantSeq 3' mRNA-Seq on an Illumina NextSeq 550 platform. Differentially expressed genes (DEGs) were identified using EdgeR with TMM+CPM normalization (fold change ≥ 1.5, p-value < 0.05). Exposure to NnK-1 resulted in 149 DEGs, with GO and IPA analyses indicating significant alterations in cell signaling and immune-related functions, including predicted inhibition of neuroinflammatory and immune response pathways associated with neurodegenerative diseases. Exposure to CBRV1-10493 identified 107 DEGs, with GO analysis revealing categories related to neurotransmission. These findings provide insights into the neuro-modulatory and immunological mechanisms of jellyfish ShK-like peptides in glioblastoma cells, and suggest their potential as candidates for therapeutic research in neurodegenerative and immune diseases.