Identification of a novel pathway in sporadic Amyotrophic Lateral Sclerosis mediated by the long non-coding RNA ZEB1-AS1

• DOI: 10.1016/j.nbd.2023.106030
• Publication Date: 2023-02-02T09:05:05Z
• Authors: Federica Rey; Erika Maghraby; Letizia Messa; Letizia Esposito; Bianca Barzaghini; Cecilia Pandini; Matteo Bordoni; Stella Gagliardi; Luca Diamanti; Manuela Teresa Ra...; Massimiliano Mazza; Gianvincenzo Zucc...; Stephana Carelli; Cristina Cereda
• Keywords: Identification

Deregulation of transcription in the pathogenesis sporadic Amyotrophic Lateral Sclerosis (sALS) is taking central stage with RNA-sequencing analyses from sALS patients tissues highlighting numerous deregulated long non-coding RNAs (lncRNAs). The oncogenic lncRNA ZEB1-AS1 strongly downregulated peripheral blood mononuclear cells patients. In addition, cancer-derived cell lines, belongs to a negative feedback loop regulation hsa-miR-200c, acting as molecular sponge for this miRNA. role has not been characterized yet, and its study could help identifying possible disease-modifying target.the implication ZEB1-AS1/ZEB1/hsa-miR-200c/BMI1 pathway was investigated multiple patients-derived cellular models (patients-derived induced pluripotent stem cells-derived neural cells) neuroblastoma line SH-SY5Y, where function inhibited via RNA interference. Molecular techniques such Real Time PCR, Western Blot Immunofluorescence were used assess dysregulation.Our results show dysregulation signaling involving ZEB1-AS1/hsa-miR-200c/β-Catenin These validated vitro on SH-SY5Y silenced expression ZEB1-AS1. Moreover, we found an increase during differentiation aberrant β-Catenin, also aggregation impact neurite length.Our support describe specifically neuronal differentiation, suggesting that impairment β-Catenin alteration phenotype are place.