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

Michela Ferraldeschi, Silvia Romano, Simona Giglio, Carmela Romano, Emanuele Morena, Rosella Mechelli, Viviana Annibali, Martina Ubaldi, Maria Chiara Buscarinu, Renato Umeton, Gabriele Sani, Andrea Vecchione, Marco Salvetti, Giovanni Ristori

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number657973
JournalFrontiers in Neurology
Publication statusPublished - May 5 2021


  • bioinformatic analysis
  • biomarkers
  • circulating miRNA
  • digital droplet PCR
  • huntington disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


Dive into the research topics of 'Circulating hsa-miR-323b-3p in Huntington's Disease: A Pilot Study'. Together they form a unique fingerprint.

Cite this