Integrated analysis of circRNA-associated ceRNA network in ischemic stroke

Area of Science:

• Biochemistry
• Genetics
• Molecular Biology

Background:

• Ischemic stroke (IS) is a leading cause of global disability and mortality.
• Circular RNAs (circRNAs) play a role in IS pathophysiology, often functioning as competing endogenous RNA (ceRNA) by sponging microRNAs (miRNAs).
• Comprehensive analysis of circRNA-mediated ceRNA networks in IS is lacking.

Purpose of the Study:

• To construct and analyze a whole transcriptome-wide circRNA-miRNA-mRNA ceRNA network associated with IS.
• To identify key regulatory axes and potential biomarkers for IS.

Main Methods:

• Expression profiles of circRNAs, miRNAs, and messenger RNAs (mRNAs) were obtained from Gene Expression Omnibus (GEO) datasets.
• Differentially expressed (DE) molecules were identified in IS patients.
• Databases like StarBase, CircBank, and mirDIP were used for target prediction to build the ceRNA network.
• Protein-protein interaction analysis identified hub genes and a core sub-network.

Main Results:

• The analysis identified 276 DEcircRNAs, 43 DEmiRNAs, and 1926 DEmRNAs.
• A ceRNA network comprising 69 circRNAs, 24 miRNAs, and 92 mRNAs was constructed.
• A core sub-network included key molecules such as hsa_circ_0011474, hsa_circ_0023110, and genes like CDKN1A, FHL2, and RPS2.

Conclusions:

• A novel ceRNA regulatory axis, hsa_circ_0011474 - hsa-miR-20a-5p/hsa-miR-17-5p - CDKN1A, was established in relation to IS.
• These findings offer new insights into IS pathogenesis.
• The identified circRNAs and pathways represent promising diagnostic and predictive biomarkers for IS.