Circulating hsa-miR-323b-3p in Huntington's Disease: A Pilot Study

Frontiers in Neurology

Gabriele Sani¹  Andrea Vecchione²  Marco Salvetti³  Giovanni Ristori⁴  Simona Giglio⁵  Martina Ubaldi⁷  Viviana Annibali⁷  Maria Chiara Buscarinu⁷  Carmela Romano⁷  Silvia Romano⁷  Emanuele Morena⁷  Rosella Mechelli⁹  Michela Ferraldeschi^1,11  Renato Umeton^1,13 

[1] 0Department of Psychiatry, Fondazione Policlinico Agostino Gemelli Istituti di Ricovero e Cura a Carattere Scientifico, Rome, Italy;1Surgical Pathology Units, Department of Clinical and Molecular Medicine, Ospedale Sant'Andrea, Sapienza University, Rome, Italy;2Istituti di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy;3Neuroimmunology Unit, Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, Rome, Italy;Department of Experimental Medicine, Policlinico Umberto i of Rome, Sapienza University, Rome, Italy;Department of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, MA, United States;Department of Neurosciences, Centre for Experimental Neurological Therapies (CENTERS), Mental Health and Sensory Organs, Sapienza University of Rome, Rome, Italy;Harvard School of Public Health, Boston, MA, United States;Istituti di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, San Raffaele Roma Open University, Rome, Italy;Massachusetts Institute of Technology, Cambridge, MA, United States;Ospedale San Giovanni Battista, ACISMOM, Rome, Italy;Section of Psychiatry, Department of Neuroscience, University Cattolica del Sacro Cuore, Rome, Italy;Weill Cornell Medicine, New York City, NY, United States;

关键词: circulating miRNA;    huntington disease;    biomarkers;    digital droplet PCR;    bioinformatic analysis;   

DOI  :  10.3389/fneur.2021.657973

来源: DOAJ

【 摘 要 】

The momentum of gene therapy in Huntington's disease (HD) deserves biomarkers from easily accessible fluid. We planned a study to verify whether plasma miRNome may provide useful peripheral “reporter(s)” for the management of HD patients. We performed an exploratory microarray study of whole non-coding RNA profiles in plasma from nine patients with HD and 13 matched controls [eight healthy subjects (HS) and five psychiatric patients (PP) to minimize possible iatrogenic impact on the profile of non-coding RNAs]. We found an HD-specific signature: downregulation of hsa-miR-98 (fold change, −1.5, p = 0.0338 HD vs. HS, and fold change, 1.5, p = 0.0045 HD vs. PP) and upregulation of hsa-miR-323b-3p (fold change, 1.5, p = 0.0007 HD vs. HS, and fold change, 1.5, p = 0.0111 HD vs. PP). To validate this result in an independent cohort, we quantify by digital droplet PCR (ddPCR) the presence of the two microRNA in the plasma of 33 HD patients and 49 matched controls (25 HS and 24 PP patients). We were able to confirm that hsa-miR-323b-3p was upregulated in HD and premanifest HD vs. HS and PP: the median values (first–third quartile) were 4.1 (0.9–10.53) and 5.8 (1.9–10.70) vs. 0.69 (0.3–2.75) and 1.4 (0.78–2.70), respectively, p < 0.05. No significant difference was found for hsa-miR-98. To evaluate the biological plausibility of the hsa-miR-323b-3p as a component of the disease pathophysiology, we performed a bioinformatic analysis based on its targetome and the huntingtin (HTT) interactome. We found a statistically significant overconnectivity between the targetome of hsa-miR-323b-3p and the HTT interactome (p = 1.48e−08). Furthermore, there was a significant transcription regulation of the HTT interactome by the miR-323b-3p targetome (p = 0.02). The availability of handy, reproducible, and minimally invasive biomarkers coming from peripheral miRNome may be valuable to characterize the illness progression, to indicate new therapeutic targets, and to monitor the effect of disease-modifying treatments. Our data deserve further studies with larger sample size and longitudinal design.

【 授权许可】

Unknown