miRNA-133 and lncRNA-H19 expressions and their relation to serum levels of PKM2 and TGF-β in patients with systemic sclerosis

Ahmed Mb Khedr; Olfat G Shaker; Mohamed Hm El-Komy; Amul M Badr; Randa Erfan

doi:10.1016/j.ncrna.2023.12.003

miRNA-133 and lncRNA-H19 expressions and their relation to serum levels of PKM2 and TGF-β in patients with systemic sclerosis

Noncoding RNA Res. 2023 Dec 20;9(1):253-261. doi: 10.1016/j.ncrna.2023.12.003. eCollection 2024 Mar.

Authors

Ahmed Mb Khedr¹, Olfat G Shaker², Mohamed Hm El-Komy³, Amul M Badr², Randa Erfan²

Affiliations

¹ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Helwan University, Ain Helwan, Cairo, Egypt.
² Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
³ Dermatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Abstract

Background and aims: Systemic sclerosis (SSc) is a common autoimmune disorder involving the skin, blood vessels, and internal organs with an elusive pathophysiology. SSc is believed to be a genetically prone T-cell-mediated autoimmune disease. miRNAs and lncRNAs were thought to be involved in the etiology of several immunological diseases including SSc. This work aimed to assess the expression of miRNA-133, lncRNA-H19, PKM2, and TGF-β levels in SSc in comparison to controls and their relationship to the clinical course and severity of disease.

Patients and methods: Fifty patients with SSc and 40 healthy age and sex-matched controls were included in this study. miRNA-133 and H19 expression levels were detected using quantitative RT-PCR while serum levels of PKM2 and TGF-β were measured using ELISA techniques. Patients' clinical data and treatments received were extracted and correlated with proteins investigated.

Results: Our results showed that miRNA-133 was significantly downregulated in SSc patients in comparison to controls (Mean + SD of SSc = 0.61 ± 0.22, Mean ± SD of HC = 0.97 ± 0.007, p = 0.003). However, there was significant upregulation of the serum expressions of all other tested biomarkers in SSc patients in comparison to controls; H19 (Mean + SD of SSc = 10.37 ± 3.13, Mean ± SD of HC = 1.01 ± 0.01, p = 0.0001), PKM2 (Mean + SD of SSc = 28.0 ± 4.84, Mean ± SD of HC = 16.19 ± 1.32, p = 0.005) and TGF-β (Mean + SD of SSc = 150.8 ± 6.36, Mean ± SD of HC = 23.83 ± 0.93, p = 0.0001). We also detected several correlations between serum levels of the investigated proteins in patients with SSc.

Conclusion: Along with TGF-β, our results show that miRNA-133, H19, and PKM2 seem to be potential contributors to SSc pathogenesis and could be promising biomarkers in the diagnosis of SSc patients. The lncRNA-H19 correlations with TGF- β, miRNA-133, and PKM2 suggest a possible influential effect of this RNA molecule on the pathogenesis of SSc.

Keywords: PKM2; Systemic sclerosis; TGF-β; lncRNA H19; miRNA-133.