Integrated Plasma and Glial Cell Evidence Indicates a Functional Role for hsa-miR-342-5p in Spinocerebellar Ataxia Type 7 and Its Potential Use as a Biomarker

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease characterized by cerebellar ataxia and retinal degeneration, caused by an abnormal expansion of CAG repeats at the <i>ATXN7</i> gene. Disease onset and progression vary among patients, underscoring the need for novel tools to improve disease monitoring. Circulating miRNAs represent a promising prognostic tool, due to their minimally invasive sampling and high stability. The aim of this study was to assess the expression of twelve circulating miRNAs associated with neurodegeneration in plasma samples from SCA7 patients and in an inducible SCA7 glial cell model. A comparison of SCA7 patients and controls revealed that nine miRNAs exhibited significantly higher expression. Furthermore, comparison of patients with different SCA7 phenotypes to controls revealed that most miRNAs were overexpressed in plasma from early-onset patients corresponding to the clinically more severe phenotype. Regarding the cell model, we identified three miRNAs that were dysregulated; however, only hsa-miR-342-5p displayed a pattern consistent with that observed in the plasma of patient. Our findings indicate that hsa-miR-342-5p is differentially expressed in the plasma of patients and the SCA7 cellular model, implying that it can serve as a biomarker and facilitate the identification of novel processes involved in SCA7.