Co-upregulation of miR-23a-3p and Kcnk5 in a denervation-induced mouse disuse model: a hypothesis-generating observation

Abstract

Abstract Objective Denervation-induced muscle disuse is accompanied by transcriptional remodeling, but ion-channel-related transcripts and accompanying microRNA responses remain incompletely characterized. This research note examined whether Kcnk5 and mmu-miR-23a-3p are co-altered in a mouse tibialis anterior denervation model and whether in silico annotation supports future validation. Results Male mice underwent unilateral sciatic denervation, with the contralateral sham-operated tibialis anterior muscle as control; tissues were analyzed 2 weeks postoperatively. Microarray profiling showed marked Kcnk5 upregulation and moderate mmu-miR-23a-3p upregulation in denervated muscle. qRT-PCR confirmed increased Kcnk5 mRNA expression normalized to Gapdh (approximately 128-fold increase; denervated 7.98 × 10⁻⁴ ± 1.64 × 10⁻⁴ vs. sham 6.24 × 10⁻⁶ ± 0.63 × 10⁻⁶, mean ± SEM; n = 6 paired samples; paired t-test, P = 0.0048). Representative KCNK5 immunohistochemistry showed visually stronger staining in denervated than in control muscle, but reliable quantification was precluded by the diffuse, cytoplasmic nature of the staining, and protein-level changes were therefore interpreted only qualitatively. Within-group correlations were weak and did not support a direct inverse relationship. TargetScanMouse and miRDB identified mouse Kcnk5 as an in silico candidate target of mmu-miR-23a-3p. These findings define a co-upregulated, hypothesis-generating candidate observation and do not comprise evidence of a regulatory axis or direct targeting.