Investigation of potential associations between four redox-related long non-coding RNAs and glutathione peroxidase in schizophrenia: a combination of bioinformatics and experimental analyses

Mahsa Khaki; Ali Massoudifar; Nahid Davoodian; Pegah Mousavi; Najmeh Davoodian; Masoumeh Mahmoudi

doi:10.1016/j.psychres.2026.117241

Investigation of potential associations between four redox-related long non-coding RNAs and glutathione peroxidase in schizophrenia: a combination of bioinformatics and experimental analyses

Psychiatry Res. 2026 May 26:364:117241. doi: 10.1016/j.psychres.2026.117241. Online ahead of print.

Authors

Mahsa Khaki¹, Ali Massoudifar², Nahid Davoodian³, Pegah Mousavi⁴, Najmeh Davoodian⁵, Masoumeh Mahmoudi⁶

Affiliations

¹ Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
² Department of Psychiatry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
³ Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran; Department of Clinical Biochemistry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. Electronic address: Nahid.Davoodian@hums.ac.ir.
⁴ Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
⁵ Research Institute of Animal Embryo Technology, Shahrekord University, Shahrekord, Iran.
⁶ Cardiovascular Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

PMID: 42247772
DOI: 10.1016/j.psychres.2026.117241

Abstract

Background: Glutathione peroxidase (GPx), a key antioxidant enzyme, shows altered activity in individuals with schizophrenia. However, the molecular mechanisms behind this alteration remain incompletely understood. In this study, we combined bioinformatics and experimental approaches to explore potential associations between redox-related long non-coding RNAs (lncRNAs) and GPx activity in schizophrenia.

Methods: We selected four redox-related lncRNAs (PVT1, NEAT1, SOX21-AS1, H19), and bioinformatics analyses predicted their potential interactions with GPX-related genes. Subsequently, we measured lncRNA expression levels in peripheral blood mononuclear cells (PBMCs) and assessed serum GPx activity in patients with acute schizophrenia.

Results: Bioinformatics analyses identified 16 candidate miRNAs putatively targeted by the selected lncRNAs and differentially expressed in schizophrenia. Further analyses identified 154 transcription factors (TFs) targeted by the candidate miRNAs that regulate GPx expression. Based on these predicted interactions, we constructed a putative RNA regulatory network comprising 3 lncRNAs, 16 miRNAs, and 154 TFs. KEGG pathway enrichment revealed significant involvement of MAPK, mTOR, Hippo, neurotrophin, and TNF signaling pathways within this network. Experimental findings showed significant upregulation of SOX21-AS1 and downregulation of PVT1 and NEAT1 in the PBMCs of patients with acute schizophrenia. Among the examined lncRNAs, PVT1 exhibited the highest potential to distinguish patients from controls. Furthermore, decreased GPx activity was observed in the serum of patients.

Conclusions: The identified GPx‑associated RNA network may contribute to redox imbalance in schizophrenia. Although the interactions are prediction‑based, this network provides a framework for future functional studies and may help identify potential biomarkers and therapeutic targets.

Keywords: Acute-phase schizophrenia; Biomarker; PBMCs; Redox imbalance; lncRNAs; microRNA.