(NVKP-16-1-2016-0017 National Heart Program) Támogató: NKFIH
(OTKA KH 125570) Támogató: NKFIH
(János Bolyai Research Scholarship)
(ÚNKP-19-4)
Szakterületek:
Számítógépes biológia
Little is known about the mechanism of prediabetes-induced cardiac dysfunction. Therefore,
we aimed to explore key molecular changes with transcriptomic and bioinformatics approaches
in a prediabetes model showing heart failure with preserved ejection fraction phenotype.
To induce prediabetes, Long-Evans rats were fed a high-fat diet for 21 weeks and treated
with a single low-dose streptozotocin at week 4. Small RNA-sequencing, in silico microRNA
(miRNA)-mRNA target prediction, Gene Ontology analysis, and target validation with
qRT-PCR were performed in left ventricle samples. From the miRBase-annotated 752 mature
miRNA sequences expression of 356 miRNAs was detectable. We identified two upregulated
and three downregulated miRNAs in the prediabetic group. We predicted 445 mRNA targets
of the five differentially expressed miRNAs and selected 11 mRNAs targeted by three
differentially expressed miRNAs, out of which five mRNAs were selected for validation.
Out of these five targets, downregulation of three mRNAs i.e., Juxtaposed with another
zinc finger protein 1 (Jazf1); RAP2C, member of RAS oncogene family (Rap2c); and Zinc
finger with KRAB and SCAN domains 1 (Zkscan1) were validated. This is the first demonstration
that prediabetes alters cardiac miRNA expression profile. Predicted targets of differentially
expressed miRNAs include Jazf1, Zkscan1, and Rap2c mRNAs. These transcriptomic changes
may contribute to the diastolic dysfunction and may serve as drug targets.
