Androgen receptor with an elongated polyglutamine tract dysregulates muscle expression of myo-miRs and of their target genes.

The elongation of the polyQ tract in the Androgen Receptor (AR) is responsible for Spinal and Bulbar Muscular Atrophy (SBMA), a neurodegenerative disease involving lower motor neurons. Patients generally present skeletal muscle atrophy with mixed myopathic alterations as well as neurogenic features of denervation in muscle biopsy. Recent studies suggested that muscle degeneration is not only due to motor neuron death, but intrinsic changes of affected muscle cells may be primarily responsible for disease onset and/or progression. Furthermore, the conditional deletion of peripheral polyQ-AR counteracts the disease. Notably, almost all aspects of skeletal muscle development/regeneration are regulated by miRNAs, and specifically by myomiRs that are selectively enriched in muscle tissue. In this study, we analyzed by RT-qPCR the expression of several myomiRs crucial for muscle development/regeneration (miR-206, miR-133a, miR-133b, and miR-1) along with some of their putative target genes (Pax7, Myog, Myod1 and Mef2a) in the skeletal muscle tissue of a knock-in SBMA mouse model at different disease stages. We confirmed the results by western blot analyses and extended the observations to the serum of human patients. Obtained data suggest that a potential regenerative response in muscle tissue of SBMA animals may be triggered during disease progression, but the dysregulation of specific myomiR/target gene pairs may account for muscle impairment and inefficient repair mechanisms