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Advisor(s)
Abstract(s)
Sickle Cell anemia (SCA) is a hereditary hemoglobinopathy with the formation of hemoglobin S, associated with severe health outcomes. Currently, induction of fetal hemoglobin (HbF) is one of the most promising therapeutic strategies. Here we aimed to assess the potential of the natural compound Quercetin, in transcriptional expression of globin and HbF regulatory/silencing genes. In this study, the K562 cell line was used as an SCA model. Cells were exposed to Quercetin at final concentrations of 0.2 and 20 µM, and Hydroxyurea (25 µg/mL) was used as a positive control. Cell viability and proliferation were assessed through trypan blue exclusion assay. Transcriptional expression was performed by RT-qPCR using specific primers. Significant differences were analyzed using a t-test. No cytotoxic effects were observed following exposure to Quercetin. The transcriptional analysis demonstrated that Quercetin affects mRNA levels of HbF regulatory/silencing genes with associated downregulation of BCL11A, MYB, KLF1, and HBB and upregulation of HBG and BGLT3, as well as alterations in the expression of miRNAs involved in HbF post-transcriptional regulation. Our results sustain Quercetin's potential as an HbF inducer with associated upregulation of HbF-activators and decreased expression of HbF-inhibitors. These data support the need for further studies in order to confirm the potential of this compound as a new therapeutic option for β -hemoglobinopathies in the future.
Description
IDI&CA-IPL/2022/miRCa/ESTeSL
Keywords
Sickle cell disease Reactivation of fetal hemoglobin Quercetin Flavonoid Hydroxyurea HbF regulatory/silencing genes IDI&CA-IPL/2022/miRCa/ESTeSL
Citation
Canteiro B, Mendes M, Jacques F, Delgadinho M, Oliveira K, Ginete C, Gomes M, Ribeiro E, Brito M, Gomes AQ. Effects of quercetin in transcriptional and post-transcriptional regulation of fetal hemoglobin. In: ENBENG 2023 – 7th IEEE Portuguese Meeting on Bioengineering, Porto, June 22-23, 2023. p. 140-3.