Study Recommends This MicroRNA as ‘Reliable Diagnostic Marker’

Blood levels of microRNA-27a found abnormally low in women with SSc

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The levels of a small RNA molecule called microRNA-27a, or miR-27a, are significantly lower in the blood of women with systemic sclerosis (SSc) compared with healthy women, a study shows.

Thus, “MiR-27a could serve as a reliable diagnostic marker for SSc,” researchers wrote, adding that the molecule “could be considered as a treatment option both for SSc and its related disorders and complications, which indeed necessitates further investigations.”

The study, “MiR-27a as a diagnostic biomarker and potential therapeutic target in systemic sclerosis,” was published in Scientific Reports. 

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Systemic sclerosis is a chronic autoimmune disease characterized by abnormal tissue scarring, or fibrosis, in the skin and several internal organs such as the heart, kidney, lungs, and gastrointestinal tract. To improve SSc diagnosis and treatment, new and specific biomarkers of the disease are needed.

“Because of the wide range of symptoms that SSc bears, diagnostic approaches for this disease are also challenging,” the researchers wrote.

MicroRNAs, or miRNAs, have emerged as potential biomarkers and therapeutic targets for a number of diseases, including SSc. These small RNA molecules work to regulate the activity of one or more genes within cells, and therefore control when, where, and how much of certain proteins is produced.

MiR-27a is a microRNA that has been implicated in cancer and idiopathic pulmonary fibrosis (IPF), two diseases which share signaling pathways with SSc.

Specifically, evidence suggests that miR-27a suppresses the TGF-beta signaling pathway, which is known to drive fibrosis in SSc and IPF. Moreover, miR-27a levels are decreased in the lungs of IPF patients and mouse models.

Given the overlapping molecular pathways involved in these conditions, a team of researchers in Iran evaluated whether miR-27a levels were altered in the blood of SSc patients.

Because of the wide range of symptoms that SSc bears, diagnostic approaches for this disease are also challenging

Study included 60 women with SSc, divided into two groups based on disease type

The analysis involved 60 women with SSc (mean age of 50.95 years) who were seen at Firouzgar Hospital, in Iran, and 20 age-matched healthy women. Half of the patients had limited SSc, while the other half had diffuse SSc.

Results showed that miR-27a levels were significantly decreased in both subsets of SSc patients compared with healthy controls. No significant differences were detected between the different types of SSc.

Further analyses indicated that a selected cut-off miR-27a level was able to accurately distinguish SSc patients from healthy individuals, with a sensitivity of 96% (true-positive rate) and specificity of 95% (true-negative rate).

This suggests that the miRNA “could be employed as a valuable diagnostic biomarker for SSc,” the researchers wrote.

Moreover, miR-27a levels were significantly lower among patients who were positive for anti-SCL70 antibodies, which are known to correlate with diffuse SSc severity and SSc lung involvement.

“This finding could suggest the potential of miR-27a for differentiating patients from healthy ones as well as utilizing it in the assessment of disease progression, although this hypothesis needs further robust examinations in much larger populations of the SSc patients to draw a comprehensive conclusion,” the team wrote.

SSc patients with certain clinical features, such as interstitial lung disease, pulmonary arterial hypertension, muscle inflammation, and digital ulcers — open sores on the fingers or toes — tended to have lower miR-27 levels than those without them, but these differences did not reach statistical significance, meaning they could be due to chance.

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Therapies to boost or mimic activity of miR-27 may be beneficial for SSc

Patients with telangiectasias — marked by dilated blood vessels near the skin’s surface — tended to have higher levels of miR-27, but this was again not a significant finding. In addition, data from five men with SSc suggested that they have higher levels of the microRNA relative to female patients.

An algorithm predicted that miR-27 might target 1,613 different genes, 67 of them known to be involved in fibrotic processes.

“It seems likely that miR-27 negatively affects molecular pathways involved in [fibrosis], such as the [TGF-beta] signaling pathway, and as a result, it could be considered an anti-fibrotic microRNA,” the researchers wrote.

“Also, it is likely that a genetic deficit or any contributing factor for SSc causes the downregulation of miR-27a thereby leading to the aberrant activation of [TGF-beta] and other signaling pathways contributing to SSc,” they added.

As such, therapies designed to boost the production or mimic the activity of miR-27 may be beneficial for SSc.

Future and larger studies are needed to confirm these findings and miR-27’s diagnostic and therapeutic value, the team noted.