Long non-coding RNA signature in beta-thalassemia major associated with prediabetes

Abstract

Introduction/Objective Functional long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) were investigated in patients with beta-thalassemia major (β-TM) and prediabetes by analyzing gene chip expression profiles, experimental evidence and bioinformatics.

Methods Total RNA was extracted after taking blood samples from patients. Microarrays were subsequently used for genetic analysis of patients with β-TM/prediabetes (n = 5) compared with healthy individuals (n = 5). Candidate lncRNAs and mRNAs were randomly validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis. Signaling associated with β-TM was identified as being associated with prediabetes based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

Results Compared with the healthy controls, 1,511 and 1,932 lncRNAs were up- and downregulated, respectively, whereas 1,128 and 752 mRNAs were up- and downregulated, respectively, in the patients with β-TM/prediabetes. Eight dysregulated lncRNA expressions were confirmed using qRT-PCR analysis, which was consistent with the microarray results. The GO and KEGG analyses showed that the intracellular anatomical structure and multicellular organismal process were the most significantly dysregulated, and the most significantly up- and downregulated pathways were herpes simplex virus type 1 infection and vascular smooth muscle contraction, respectively.

Conclusion This study preliminarily determined that the pathophysiology of aberrant glucose homeostasis in β-TM may be linked to the abnormal expression of lncRNAs and mRNAs, deepening the understanding of molecular mechanisms in β-TM complicated by prediabetes.

Keywords: microarray analysis; long non-coding RNAs; beta-thalassemia major; mRNA; prediabetes