The lncRNAs/miR-30e/CHI3L1 Axis Is Dysregulated in Systemic Sclerosis

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Systemic sclerosis (SSc) is an autoimmune disease with unknown causes and difficult treatments.
• Dysregulation of protein coding and non-coding RNAs occurs during SSc development.
• Chitinase-3 like protein 1 (CHI3L1), an inflammation marker, is elevated in SSc patients.

Purpose of the Study:

• To investigate a potential regulatory axis controlling CHI3L1 expression in SSc.
• To identify specific microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) involved in CHI3L1 regulation.
• To explore the role of lncRNAs as decoys for miRNAs implicated in SSc pathogenesis.

Main Methods:

• In silico analysis to select candidate miRNAs and lncRNAs potentially regulating CHI3L1.
• Quantitative real-time PCR (RT-qPCR) to measure lncRNA expression in white blood cells (WBCs) and plasma.
• TagMan assays to quantify miRNA expression levels in WBCs and plasma from SSc patients and healthy controls.

Main Results:

• miR-30e-5p and miR-30a-5p were significantly downregulated in SSc patients' WBCs and plasma, respectively.
• Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and Nuclear enriched abundant transcript 1 (NEAT1) lncRNAs were upregulated in SSc patients' WBCs.
• Upregulated MALAT1 and NEAT1 may correlate with downregulated miR-30e-5p and miR-30a-5p, potentially increasing CHI3L1 levels.

Conclusions:

• A novel regulatory axis involving lncRNAs (MALAT1, NEAT1) and miRNAs (miR-30e-5p, miR-30a-5p) is proposed in Systemic Sclerosis.
• MALAT1 and NEAT1 may function as decoys for miR-30e-5p and miR-30a-5p, contributing to elevated CHI3L1 in SSc.
• This regulatory axis offers potential therapeutic targets for managing SSc and its associated inflammation.