Estudio del papel de miR-148a en la regulación de genes del metabolismo lipídico y la adipogénesis

Abstract

This research demonstrates the functionality of single nucleotide polymorphism (SNP) rs12720763, located in the APOB 3'UTR region, although the bioinformatic prediction that foresaw the loss of the binding site of miR-148a-5p, one of the mature miRNAs of miR-148a, for one of the alleles of the SNP in the 3'UTR region has not been demonstrated. This work shows that inhibition of both miR-148a-3p and miR-148a-5p, causes an increase in APOB levels in HepG2 cells which could lead to higher levels of LDL cholesterol (cLDL). The results show that inhibition of miR-148a-3p in 3T3-L1 cells causes inhibition of the canonical WNT pathway and increased expression levels in markers of adipogenesis when these cells are differentiated into adipocytes. In turn, the nuclear receptor NR5A2 upregulates expression levels of miR-148a-3p in 3T3-L1 preadipocytes and has an antiadipogenic effect on these cells. Finally, it was shown that the SNP rs4722551, located in the promoter region of miR-148a and associated with body mass index (BMI) in a cohort of Cantabria, is a functional SNP and is located on an upregulation site.