Related Experiment Video
Updated: Apr 19, 2026
Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents
Published on: August 10, 2018
Downregulation of miRNAs Accompanies Increased HERV-K (HML-2) Expression in Amyotrophic Lateral Sclerosis
Elena Rita Simula1, Marta Garcia-Montojo2,3, Mattia Canu4
1Department of Biomedical Sciences, Division of Microbiology and Virology, University of Sassari, Sassari, Italy.
Abstract:
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease with limited treatments. Evidence suggests that reactivation of the HERV-K (HML-2) subgroup contributes to its pathogenesis. This study explores the role of microRNAs (miRNAs) in regulating HML-2 expression. We identified dysregulated miRNAs in ALS and, among them, those predicted to target the HML-2 transcript. The expression levels of selected miRNAs were validated in peripheral blood leukocytes of ALS individuals and healthy controls. Co-transfection experiments were then performed to determine the regulatory potential of these miRNAs on HML-2 expression. We found that the HML-2 envelope gene expression levels were elevated in peripheral blood mononuclear cells of ALS individuals compared to controls (p = 0.02), and they negatively correlated with the levels of previously identified miRNAs, which were downregulated in patients compared to healthy controls (miR-15a-3p, p = 0.04; miR-15a-5p, p = 0.01; miR-150-5p, p = 0.001; miR-182-5p, p = 0.012; miR-192-3p, p = 0.034; miR-221-3p, p = 0.011), except miR-181a-2-3p that was upregulated in ALS compared to controls (p = 0.006). Among these miRNAs, we found, by co-transfection, that miR-182-5p and miR-221-3p were capable of binding the HML-2 transcript. This interaction resulted in a significant downregulation of the expression of its genes, with a pronounced effect observed on the envelope gene. Our findings suggest a link between miRNAs and HML-2 expression. In particular, the observed increase in HML-2 levels in ALS may result from the downregulation of key miRNAs, such as miR-221, that normally help restrain HML-2 expression under physiological conditions.
Insights
Amyotrophic lateral sclerosis (ALS) involves increased Human Endogenous Retrovirus K (HERV-K) expression, potentially due to decreased microRNAs (miRNAs). Specific miRNAs, like miR-221, normally regulate HERV-K, but their downregulation in ALS patients may allow HERV-K reactivation.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with limited therapeutic options.
- Reactivation of the Human Endogenous Retrovirus K (HERV-K) HML-2 subgroup is implicated in ALS pathogenesis.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are increasingly recognized for their role in disease.
Purpose of the Study:
- To investigate the role of miRNAs in regulating HERV-K (HML-2) expression in ALS.
- To identify specific miRNAs dysregulated in ALS patients and their potential to target HERV-K transcripts.
- To elucidate the functional relationship between miRNAs and HERV-K expression in the context of ALS.
Main Methods:
- Identification of dysregulated miRNAs in ALS patient samples.
- Bioinformatic prediction of miRNA targets on the HERV-K transcript.
- Validation of miRNA expression in peripheral blood leukocytes from ALS patients and healthy controls.
- Co-transfection experiments to assess the regulatory effect of miRNAs on HERV-K expression.
Main Results:
- HERV-K envelope gene expression was significantly elevated in ALS patients compared to controls.
- Several miRNAs, including miR-15a-3p, miR-15a-5p, miR-150-5p, miR-182-5p, miR-192-3p, and miR-221-3p, were downregulated in ALS patients.
- miR-182-5p and miR-221-3p demonstrated the ability to bind the HERV-K transcript, leading to significant downregulation of its gene expression, particularly the envelope gene.
- miR-181a-2-3p showed increased expression in ALS patients.
Conclusions:
- A significant link exists between miRNA dysregulation and aberrant HERV-K expression in ALS.
- The downregulation of specific miRNAs, such as miR-221, may contribute to the increased HERV-K levels observed in ALS.
- These findings suggest that targeting miRNA-HERV-K interactions could represent a novel therapeutic strategy for ALS.
More Related Videos
09:40Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
09:13Hypoxia Alters miRNAs Levels Involved in Non-Mendelian Inheritance of Autism Spectrum Disorder in Mice
Published on: July 11, 2025
Related Concept Videos
01:22MicroRNAs
01:22MicroRNAs
01:22MicroRNAs
01:37Neural Regulation