Cross-organ communication based on non-coding RNA networks leads to cognitive dysfunction in mice.

Area of Science:

• Genomics
• Molecular Biology
• Systems Biology

Background:

• Competitive endogenous RNAs (ceRNAs) play a crucial role in disease pathogenesis through their interactions.
• Understanding cross-organ molecular interactions is vital for comprehending complex diseases.
• FTSJ1 deficiency is linked to cognitive dysfunction and other phenotypes.

Purpose of the Study:

• To investigate the multi-omics, cross-organ regulatory mechanisms underlying cognitive dysfunction in FTSJ1 deficiency.
• To construct organ-specific ceRNA networks in Ftsj1-deficient mice.
• To identify potential ncRNA biomarkers for FTSJ1 deficiency.

Main Methods:

• Multi-omics analysis of mRNA and multiple ncRNA species (miRNAs, lncRNAs, circRNAs) in Ftsj1-deficient and wild-type mice.
• Construction of organ-specific ceRNA networks (brain, heart, kidney, liver, spleen).
• Validation of ncRNA biomarkers using degradome sequencing and qRT-PCR.

Main Results:

• FTSJ1 deficiency significantly altered gene expression in the liver and kidney, particularly affecting fatty acid metabolism.
• A prominent ceRNA network involving four hub-miRNAs and acyl-CoA-related genes was identified in the liver and kidney.
• Brain tissues exhibited minimal gene expression changes, suggesting indirect regulatory pathways contributing to cognitive dysfunction.

Conclusions:

• Cognitive impairment in FTSJ1 deficiency is associated with metabolic disturbances and ceRNA crosstalk along liver-brain and kidney-brain axes.
• Multi-omics, cross-organ analyses are essential for understanding gene-associated intellectual disabilities.
• Findings highlight the importance of ceRNA networks in developing therapeutics and biomarkers for cognitive disorders.