PhD Scientific Days 2026

Poster Session 1.A - Molecular Medicine

Fatty Acid-Dependent Modulation of MicroRNA Expression and miR-1269a-Mediated Regulation of H6PD in HepG2 Cells

Name of the presenter

Orosz, Gabriella

Institute/workplace of the presenter

Semmelweis University, Department of Molecular Biology, Budapest, Hungary

Authors

Gabriella Orosz¹, Veronika Zámbó¹, Miklós Csala¹, Éva Kereszturi¹
1: Semmelweis University, Department of Molecular Biology, Budapest, Hungary

Text of the abstract

Elevated circulating fatty acid (FA) levels play a key role in cellular damage and the development of metabolic syndrome. Both FAs and microRNAs are critical regulators of lipid homeostasis; however, the mechanisms by which different saturated and unsaturated FAs modulate lipid metabolism through altering microRNA expression profiles remain poorly understood.
We aimed to investigate the effects of saturated and cis- and trans-unsaturated FAs on microRNA expression profiles. Furthermore, we sought to identify the targets of FA-sensitive microRNAs using in silico and in vitro methods.
Total RNA was isolated from HepG2 cells treated with palmitate, oleate, or elaidate, and microRNA sequencing was performed after quality control. After multiple testing, 14 microRNAs that showed significant expression changes in the presence of a fatty acid were identified; several of them were validated by qPCR. Putative target genes were identified using three independent databases. Among 38 predicted targets, three lipid metabolism-related proteins (CEBPB, FASN, and H6PD) were selected for further analysis by qPCR and immunoblotting.
While H6PD mRNA levels did not change, its protein levels were significantly increased following FA treatments, suggesting post-transcriptional regulation. Our observation is consistent with the predicted presence of the hsa-miR-1269a binding site in the 3’UTR region of H6PD and with the significantly reduced expression of this microRNA in the presence of palmitate. The functional interaction between miR-1269a and the H6PD 3′UTR was further confirmed in an in vitro luciferase reporter system.
Our results show that different fatty acids can significantly alter the microRNA expression profile of HepG2 cells and indicate that fatty acid-dependent regulation of H6PD is likely mediated by miR-1269a.

This work was supported by NKFIH (FK138115 and PD142709) and by the University Research Scholarship Programme (2025-2.1.1-EKÖP-2025-00014).