Hibernation-Induced microRNA Expression Promotes Signaling Pathways and Cell Cycle Dysregulation in Ictidomys tridecemlineatus Cardiac Tissue.
W Aline Ingelson-FilpulaKenneth B StoreyPublished in: Metabolites (2023)
The thirteen-lined ground squirrel Ictidomys tridecemlineatus is a rodent that lives throughout the United States and Canada and uses metabolic rate depression to facilitate circannual hibernation which helps it survive the winter. Metabolic rate depression is the reorganization of cellular physiology and molecular biology to facilitate a global downregulation of nonessential genes and processes, which conserves endogenous fuel resources and prevents the buildup of waste byproducts. Facilitating metabolic rate depression requires a complex interplay of regulatory approaches, including post-transcriptional modes such as microRNA. MicroRNA are short, single-stranded RNA species that bind to mRNA transcripts and target them for degradation or translational suppression. Using next-generation sequencing, we analyzed euthermic vs. hibernating cardiac tissue in I. tridecemlineatus to predict seven miRNAs (let-7e-5p, miR-122-5p, miR-2355-3p, miR-6715b-3p, miR-378i, miR-9851-3p, and miR-454-3p) that may be differentially regulated during hibernation. Gene ontology and KEGG pathway analysis suggested that these miRNAs cause a strong activation of ErbB2 signaling which causes downstream effects, including the activation of MAPK and PI3K/Akt signaling and concurrent decreases in p53 signaling and cell cycle-related processes. Taken together, these results predict critical miRNAs that may change during hibernation in the hearts of I. tridecemlineatus and identify key signaling pathways that warrant further study in this species.
Keyphrases
- cell cycle
- cell proliferation
- pi k akt
- signaling pathway
- cell cycle arrest
- depressive symptoms
- transcription factor
- genome wide
- sleep quality
- binding protein
- left ventricular
- copy number
- epithelial mesenchymal transition
- induced apoptosis
- gene expression
- poor prognosis
- long non coding rna
- genome wide identification
- heavy metals
- oxidative stress
- heart failure
- drinking water
- atrial fibrillation
- drug induced
- diabetic rats
- risk assessment
- genome wide analysis
- long noncoding rna
- endoplasmic reticulum stress
- sewage sludge
- municipal solid waste