Faculdade de Ciências
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Browsing Faculdade de Ciências by advisor "Alexandre, Daniela de Jesus"
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- Effects of G-quadruplex structures formation in miRNA expression associated with lung cancerPublication . Polido, Joana Curado; Cruz, Carla Patricia Alves Freire Madeira da; Baptista, Pedro Viana; Alexandre, Daniela de JesusLung cancer (LC) is a growing health issue. Characterized by the aggressive profile and late presentation, it ranks first as the deadliest cancer worldwide, requiring novel therapeutic approaches and biomarkers to improve the prognosis. MicroRNAs (miRNAs or miR) are actively implicated in the inhibition of gene expression, leading to pathologies when dysregulated. In this way, they are promising targets in diagnosis but also therapy by restoring the endogenous levels. MiR-3196 and miR-193a-5p/3p are aberrantly expressed in LC, affecting the cancer cell’s apoptosis, proliferation, and migration. The G-quadruplex (G4) is a non-canonical secondary structure capable of structurally interfering with the enzymatic maturation and target binding in miRNAs, acting as a potential tool for miRNA silencing. The current dissertation determines the expression and therapeutic potential of miR-3196 and miR-193a-3p/5p in peripheral blood mononuclear cells (PBMCs) and LC cell lines and evaluates the miRNA-silencing by the G4 structure stabilization within the precursor sequences. Overall, the abnormal profile of both miRNAs and their suitability as targets was observed. Biophysical evidence confirmed the folding of stable parallel G4 structures in the pre-miRNAs, greatly stabilized by the ligand C8-NH2. In cells, incubation with the ligand did not reveal a G4-mediated effect on the maturation. Hence, further research is required to validate the results and assess this hypothesis as an anti-cancer strategy.