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miR-26a and miR-125b as a promising biomarker for the diagnosis of RRMS patients

This study demonstrates that the significantly elevated expression levels of miR-26a and miR-125b in the peripheral blood mononuclear cells of Iranian patients with relapsing-remitting multiple sclerosis suggest their potential utility as diagnostic biomarkers for the disease.

Original authors: Mehran Mohammadzadeh, Parastoo Sadaat Jalali, Venus Zafari, Soghra Bornehdeli, Dariush Shanehbandi, Sheida Shaafi, Saeed Ghazanfari Amlashi

Published 2026-08-14

📖 4 min read☕ Coffee break read

CC BY 4.0

Original authors: Mehran Mohammadzadeh, Parastoo Sadaat Jalali, Venus Zafari, Soghra Bornehdeli, Dariush Shanehbandi, Sheida Shaafi, Saeed Ghazanfari Amlashi

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

Imagine your body as a bustling city where billions of tiny workers keep everything running smoothly. Sometimes, the city's security system gets a little confused and starts attacking its own buildings instead of real intruders. This is what happens in Multiple Sclerosis (MS), a condition where the immune system mistakenly damages the protective coating of nerves in the brain and spinal cord. For years, doctors have been trying to find a simple, non-invasive way to spot this trouble early, like finding a smoke detector that goes off before the fire even starts.

Enter the world of microRNAs. Think of these as tiny, invisible "volume knobs" or "traffic controllers" floating inside your cells. They are short strands of genetic material that don't build proteins themselves but instead tell other genetic instructions when to turn up the volume, when to turn it down, or when to stop completely. In a healthy city, these knobs are set just right. But in MS, some of these knobs get stuck in the wrong position, causing chaos. Scientists have been hunting for specific "broken knobs" that could serve as a signature for the disease, hoping to use a simple blood test to diagnose MS without needing complex brain scans or spinal taps.

This study, conducted by researchers in Iran, decided to check the "volume settings" of two specific genetic knobs, named miR-26a and miR-125b, in the blood of people with MS. They gathered blood samples from 150 people: 75 who had been diagnosed with a common form of MS called Relapsing-Remitting MS (RRMS), and 75 healthy people who had no history of the disease. Using a high-tech lab technique called qRT-PCR (which is like a super-sensitive microphone that can hear the faintest whispers of these genetic knobs), the team measured how much of each knob was present in the blood cells.

The results were quite clear. The researchers found that the "volume" of both miR-26a and miR-125b was turned up significantly higher in the patients with MS compared to the healthy group. It wasn't just a tiny difference; the increase was statistically strong, with the chance of this happening by random luck being extremely low (less than 1 in 10,000 for miR-26a and about 1 in 50 for miR-125b). To see if these findings could actually help diagnose the disease, the team ran a statistical test called a ROC curve analysis. This test acts like a quality check for a detective's tool, measuring how good it is at telling a sick person from a healthy one. The "score" for miR-26a was 0.678, and for miR-125b, it was 0.7. While these numbers suggest these knobs are promising clues, they aren't perfect detectives yet; they are better than flipping a coin, but they aren't a magic wand that solves the mystery instantly.

Interestingly, the study also looked to see if the amount of these knobs changed based on how sick the patients were, how long they had the disease, or their age. The answer was a bit of a "nope." The levels of miR-26a and miR-125b didn't seem to correlate with how disabled a patient was or how long they had been sick. This suggests that these knobs might be a general signal that the disease is present, rather than a gauge that measures exactly how bad the damage is at any given moment.

In the end, the authors conclude that these two genetic knobs are likely useful as part of a diagnostic toolkit for MS, but they aren't the whole story yet. The study suggests that abnormal levels of miR-26a and miR-125b could serve as a red flag in the blood, but more research is needed to confirm exactly how they work and to see if they can be relied upon in the real world. For now, they are a very promising lead in the search for a simpler way to catch this tricky disease.

Technical Summary: miR-26a and miR-125b as Promising Biomarkers for RRMS Diagnosis

Problem Statement
Multiple Sclerosis (MS) is a leading cause of non-traumatic neurological disability in young people, characterized by inflammatory demyelination within the central nervous system (CNS). While the pathophysiology involves complex mechanisms such as proinflammatory cytokine release, blood-CSF barrier permeability changes, and axonal swelling, a reliable index for the primary diagnosis of MS remains a significant challenge. Current diagnostic methods often rely on clinical criteria and imaging, prompting a search for less invasive, blood-derived biomarkers. Recent research has highlighted the dysregulation of microRNAs (miRNAs)—small non-coding RNAs of 21–25 nucleotides—in neurodegenerative diseases. Specifically, miR-26a and miR-125b have been implicated in MS pathogenesis, yet their specific expression profiles and diagnostic utility in the Iranian population (Azari individuals) required further evaluation.

Methodology
This study employed a case-control design involving 150 blood specimens: 75 from patients diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS) and 75 from healthy individuals.

Subject Selection: RRMS patients were recruited from Imam Reza Hospital in Tabriz, Iran, between 2019 and 2020, diagnosed according to McDonald criteria. The control group consisted of individuals with no prior medical or mental illness history. Demographic data, including age, gender, disease onset, duration, and Expanded Disability Status Scale (EDSS) scores, were recorded.
Sample Processing: Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood using the Ficoll-Hypaque density gradient technique.
RNA Analysis: Total RNA was extracted from approximately 200 µL of PBMCs using TRIzol reagent. Following quality assessment via NanoDrop spectrophotometry, 1,000 ng of RNA was reverse-transcribed into cDNA using the miRCURY RNA isolation kit.
Quantification: Expression levels of miR-26a and miR-125b were quantified using qRT-PCR on a LightCycler® 96 Instrument. U6 snRNA served as the reference gene for normalization, with expression calculated via the $2^{-\Delta CT}$ method.
Statistical Analysis: Data were analyzed using GraphPad Prism (v6.0). The Mann-Whitney U test assessed differences in expression levels between groups, while Spearman's correlation (Pearson's test mentioned in text, but Table 3 uses $\rho$ ) evaluated relationships between miRNA levels and clinical parameters (EDSS, age, disease duration). ROC curve analysis determined diagnostic accuracy.

Key Results
The study observed significant upregulation of both target miRNAs in RRMS patients compared to healthy controls:

Expression Levels: miR-26a expression was significantly increased ( $P = 0.0001$ ), and miR-125b expression was also significantly higher in the patient group ( $P = 0.019$ ).
Diagnostic Performance: Receiver Operating Characteristic (ROC) curve analysis indicated moderate diagnostic potential. miR-26a yielded an Area Under the Curve (AUC) of 0.678 ( $P = 0.0001$ ), while miR-125b achieved an AUC of 0.70 ( $P = 0.0001$ ).
Clinical Correlations: No statistically significant correlation was found between the expression levels of miR-26a or miR-125b and clinical variables, including EDSS scores, age of disease onset, disease duration, or patient age.

Significance and Claims
The authors posit that the abnormal upregulation of miR-26a and miR-125b in the peripheral blood of RRMS patients suggests their potential utility as diagnostic biomarkers for Multiple Sclerosis. The study supports existing literature indicating that miR-26a interacts with the 3'-UTR of SLC1A1 and regulates immune system development, while miR-125 family members are involved in oligodendrocyte maturation and demyelination processes.

However, the paper maintains a modest tone regarding its conclusions. It explicitly states that while these miRNAs show promise as screening tools, the exact mechanisms of action and their specific target genes in MS pathology remain unclear. The authors emphasize that further comprehensive research is necessary to confirm these findings, elucidate the precise molecular mechanisms, and validate their role as definitive diagnostic markers before clinical application. The study concludes that these miRNAs are likely candidates for diagnosis but requires corroboration through additional investigation.

Technical Summary: miR-26a and miR-125b as Promising Biomarkers for RRMS Diagnosis

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