20.500.12556/DiRROS-19241 Aberrantly expressed hsa_circ_0060762 and CSE1L as potential peripheral blood biomarkers for ALS Amyotrophic lateral sclerosis (ALS) is a rapidly progressive adult-onset neurodegenerative disease that is often diagnosed with a delay due to initial non-specific symptoms. Therefore, reliable and easy-to-obtain biomarkers are an absolute necessity for earlier and more accurate diagnostics. Circular RNAs (circRNAs) have already been proposed as potential biomarkers for several neurodegenerative diseases. In this study, we further investigated the usefulness of circRNAs as potential biomarkers for ALS. We first performed a microarray analysis of circRNAs on peripheral blood mononuclear cells of a subset of ALS patients and controls. Among the differently expressed circRNA by microarray analysis, we selected only the ones with a host gene that harbors the highest level of conservation and genetic constraints. This selection was based on the hypothesis that genes under selective pressure and genetic constraints could have a major role in determining a trait or disease. Then we performed a linear regression between ALS cases and controls using each circRNA as a predictor variable. With a False Discovery Rate (FDR) threshold of 0.1, only six circRNAs passed the filtering and only one of them remained statistically significant after Bonferroni correction: hsa_circ_0060762 and its host gene CSE1L. Finally, we observed a significant difference in expression levels between larger sets of patients and healthy controls for both hsa_circ_0060762 and CSE1L. CSE1L is a member of the importin β family and mediates inhibition of TDP-43 aggregation; the central pathogenicity in ALS and hsa_circ_0060762 has binding sites for several miRNAs that have been already proposed as biomarkers for ALS. In addition, receiver operating characteristics curve analysis showed diagnostic potential for CSE1L and hsa_circ_0060762. Hsa_circ_0060762 and CSE1L thus represent novel potential peripheral blood biomarkers and therapeutic targets for ALS. amyotrophic lateral sclerosis ALS circRNA biomarker peripheral blood biomarker hsa_circ_0060762 CSE1L biomedicine amiotrofična lateralna skleroza ALS circRNA biomarker biomedicina true false true Angleški jezik Slovenski jezik Neznano 2024-07-12 03:37:22 2024-07-12 11:19:11 2024-07-13 03:49:20 0000-00-00 00:00:00 2023 0 0 Ostali avtorji: Massimo Mezzavilla, Ana Dolinar, Blaž Koritnik and Damjan Glavač; Nasl. z nasl. zaslona; Opis vira z dne 8. 8. 2023; str. [1]-10 art. 1316 iss. 5 May 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2023-04-28 577 2227-9059 10.3390/biomedicines11051316 160876291 https://doi.org/10.3390/biomedicines11051316 1 49891f09-3fef-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26499 RAZ_Ravnik-Glavac_Metka_2023.pdf RAZ_Ravnik-Glavac_Metka_2023.pdf 1 58D4849EC944B89500B66EA667DAE017 08807d99a4ae7cc604b5d0b8396647db4da69c5e5b89b4cab94127bbb2cd1a3f 0545b19a-4030-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26576 Nacionalni inštitut za biologijo 0 0 0