Banca de DEFESA: Sabrina Simplício de Araujo Romero Ferrari

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : Sabrina Simplício de Araujo Romero Ferrari
DATE: 05/12/2025
TIME: 14:30
LOCAL: A definir.
TITLE:

Expression of the Regulatory Network of miR-7, miR-671, Cyrano (OIP5-1AS), and CDR1as in an In Vitro Model of MPP+-Induced Dopaminergic Neurodegeneration

KEY WORDS:

miR-7, miR-671, Cyrano, CDR1as, Parkinson's disease

PAGES: 100
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

Parkinson's Disease (PD) is a chronic neurodegenerative disorder that affects movement and may also impair cognition. It is pathologically characterized by the loss of dopaminergic neurons in the nigrostriatal network and by the formation of Lewy bodies, resulting from alpha-synuclein aggregation and intracellular deposition. Regulatory RNAs, including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs), are functionally related and involved in the pathophysiology of PD. Cyrano is an lncRNA (also known as OIP5-AS1) that participates in embryonic development, acting in processes such as proliferation, apoptosis, and mitosis, and may be involved in neurological diseases, inflammatory disorders, and cancer; one of its important molecular functions is the ability to interact with miR-7, potentially promoting its degradation due to a complementary binding site. The circular RNA CDR1as (Cerebellar degeneration-related protein 1 antisense RNA) is one of the most well-characterized circRNAs, highly expressed in the mammalian brain, with over 70 binding sites for miR-7, acting as a miR-7 "reservoir." Another relevant microRNA is miR-671, which contributes to the pathogenesis of several diseases, including PD; this microRNA negatively regulates the CDR1as gene via AGO2, therefore making it part of the miR-7 regulatory network, along with CDR1as and Cyrano. The present study aimed to investigate the expression of Cyrano, CDR1as, miR-7, and miR-671 in an in vitro model of MPP+-induced dopaminergic neurodegeneration, using SH-SY5Y cells. Exposure of SH-SY5Y cells to MPP+ for 24 hours caused a dose-dependent reduction in cell viability of 87.30%, 81.20%, 58.7%, 34.2%, and 15% at the respective concentrations of 0.25 mM, 0.5 mM, 1 mM, 2 mM, and 4 mM. Indeed, a significant increase in oxidative stress was also observed at MPP+ concentrations of 0.5 mM, 1.0 mM, and 2.0 mM, along with morphological changes typical of apoptosis, such as nuclear condensation and fragmentation. The apoptotic nuclei count revealed that apoptosis was dose-dependent (P<0.05). Finally, RT-qPCR expression analysis showed a significant dysregulation of the regulatory network in the MPP+-exposed groups. We observed a 2.04-fold increase in CDR1as expression (P=0.0083) and a 0.439-fold and 0.613-fold reduction in miR-671 and miR-7 expression, respectively (P<0.05). Cyrano, in contrast, did not show a statistically significant difference in gene expression. The results demonstrate that MPP+- induced toxicity affects the miR-7 regulatory network and suggest the involvement of these ncRNAs in cell viability loss, indicating them as potential biomarkers and promising targets for neuroprotective therapies. Further silencing studies and analysis in patient samples are necessary to confirm the role of these RNAs in the degeneration of dopaminergic neurons.

COMMITTEE MEMBERS:
Externo ao Programa - 1307139 - FABIANO JOSE FERREIRA DE SANT ANA - nullExterno à Instituição - FERNANDO FRANCISCO BORGES RESENDE - UNICEPLAC
Externo ao Programa - ***.731.541-** - RAPHAEL SEVERINO BONADIO - PADOVA
Presidente - 1127261 - RICARDO TITZE DE ALMEIDA