Levels of 4 microRNAs in blood may help diagnose PAH, researchers say

Small RNA molecules found at different levels in patients vs. healthy people

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Four microRNAs (miRNAs) — small RNA molecules that regulate protein production — were found at different levels in blood samples from people with pulmonary hypertension (PH) compared with healthy people, a small study reported.

Levels of two of these miRNAs were significantly higher in the PH patients versus the healthy individuals, while the levels of the other two were significantly lower.

According to the researchers, these findings have particular significance for patients with a rare type of PH, called pulmonary arterial hypertension (PAH), in which narrowing of the small blood vessels that transport blood through the lungs restricts blood flow, causing high blood pressure or hypertension in these arteries.

Assessing the levels of these four microRNAs “could be used as clinical diagnostic biomarkers for pulmonary arterial hypertension,” the researchers wrote.

The study, “Whole-genome microRNA sequencing analysis in patients with pulmonary hypertension,” was published Frontiers in Genetics.

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MicroRNA findings could lead to new treatments for PH

Commonly called miRNAs, microRNAs are a special class of short RNA molecules capable of regulating gene activity. They are tissue-specific and temporally expressed, meaning that the activation of their respective genes occurs at specific times. Normally, miRNAs suppress protein production by targeting the messenger RNA, the molecule derived from DNA that serves as a blueprint to make proteins.

Recent studies suggest a role of miRNA in signaling pathways implicated in pulmonary hypertension — supporting their potential as disease biomarkers.

“Detecting and regulating the expression [gene activity] of PH-associated miRNAs may help prevent or treat PH,” the researchers wrote.

“Therefore, miRNAs are important starting points to identify novel therapeutic targets for PH,” the team wrote.

However, no microRNAs that could serve as diagnostic or prognostic biomarkers in PAH have been identified.

Now, researchers in China compared the levels of miRNAs in blood samples from four PH patients and four healthy people. The team conducted a genome-wide miRNA sequencing analysis, a comprehensive approach that involves scanning the entire genome.

The results revealed that the levels of 136 miRNAs were significantly different in PH patients when compared with samples from healthy participants. Specifically, a total of 68 miRNAs were produced at higher levels, or upregulated, in PH patients, while 68 were downregulated, or produced at lower levels than in the healthy controls.

These findings prove the reliability and validity of our data and provide evidence that these four differentially expressed miRNAs are potential diagnostic markers for PH.

The top pathways related to the differentially expressed genes were involved in processes such as cell signaling, metabolism, immune function, and the endocrine (hormone-related) system.

Further analysis confirmed the differential expression of four miRNAs in samples from PH patients relative to healthy controls. Two miRNAs — hsa-miR-1304-3p and hsa-miR-490-3p — were significantly increased, whereas the other two — hsa-miR-11400 and hsa- miR-31-5p — were significantly reduced.

Overall, “these findings prove the reliability and validity of our data and provide evidence that these four differentially expressed miRNAs are potential diagnostic markers for PH,” the researchers wrote.

The team concluded that these results “provide a new reference and basis for future in-depth investigation of the specific miRNA-related mechanisms in PH.”

A Conversation With Rare Disease Advocates