microRNAs are potentially regulating the survivin gene in PBMCs from systemic sclerosis patients

Abstract

Background: Survivin is an important anti-apoptotic protein and is involved in increasing auto-reactivity during the autoimmune diseases like systemic sclerosis (SSc).

Aims: In the current study, we investigate the expression level of total survivin (survivin-TS) and its three important variants alongside with evaluation of the expression level of important microRNAs (miRNAs) that are involved in survivin expression regulation.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 50 healthy controls, 25 diffuse cutaneous SSc (DcSSc), and 25 limited cutaneous SSc (LcSSc) patients. RNA was extracted and single-strand cDNA was synthesized. Quantitative real-time PCR was used to evaluate the expression level of survivin-TS and its variants as well the miRNAs.

Results: Overexpression of survivin-2B and downregulation of survivin wild-type (survivin-WT) were found in total-SSc patients; however, expression level of survivin-TS had no significant difference. The expression levels of miR-335-5p, miR-485-5p, miR-16-5p, miR-150-5p, miR-34a-5p, miR-218-5p and miR-708-5p were higher in total-SSc patients. Significantly negative correlations were found between transcript levels of miR-150-5p, miR-16-5p, and miR-485-5p with survivin-TS mRNA expression.

Conclusion: Survivin variants had altered expression in total-SSc patients. In addition, miRNAs might potentially and negatively regulate the survivin-TS expression. Altered expression of survivin, regulated by miRNAs, may result in apoptosis resistance and auto-reactivity in lymphocytes from patients and have important roles in SSc pathogenicity.

Keywords:

• Systemic sclerosis
• apoptosis
• survivin
• immune tolerance
• miRNA

Acknowledgements

The authors are grateful of patients and healthy individuals who contributed to the accomplishing of the study.

Ethical approval

The current study was reviewed and approved by Human Research Ethics Committee of Tehran University of Medical Science and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Written informed consent forms were obtained from all study subjects.

Author’s contributions

HRE performed the experiments and prepared the draft of the paper. FG introduced the patients and read the manuscript critically. SA analyzed the data, participated in manuscript preparation. HK introduced the patients and read the manuscript. FF introduced the patients and read the manuscript. AJ introduced the patients and read the manuscript critically. MM developed the main idea, designed the work, and read the manuscript critically. All authors have read and approved the manuscript.

Conflict of interest

None.

Data availability statement

Data are available upon request.

Additional information

Funding

This study was supported by a grant from Deputy of Research, Tehran University of Medical Sciences [Grant No. 96-01-41-34784].