| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 415.81 KB | Adobe PDF |
Orientador(es)
Resumo(s)
Introdução – As hemoglobinopatias constituem um dos grupos de doenças monogénicas mais prevalentes a nível mundial. Atualmente, um dos tratamentos disponíveis consiste na indução farmacológica da hemoglobina fetal (HbF) através de vários compostos químicos, sendo o mais comum a hidroxiureia (HU). Contudo, o seu custo elevado em países subdesenvolvidos e o seu perfil de segurança limitam a utilização deste composto. Assim, é essencial a descoberta de novos compostos indutores de HbF com menos efeitos secundários e de fácil acesso, como é o caso dos compostos naturais (e.g., extrato de folha de Carica papaya L.). Objetivo – Avaliar o efeito da exposição de células K562 (linha celular humana imortalizada de leucemia mieloide) ao extrato metanólico das folhas de Carica papaya L. (EMFCP) ao nível da expressão dos miRNAs envolvidos na regulação da HbF. Métodos – As células K562 foram expostas durante 24 horas ao EMFCP (0,5; 50 e 100μg/mL) e a HU (25μg/mL). A análise da expressão dos miRNAs envolvidos na regulação da HbF (miR-486-3p, miR-34a-5p, miR-210-5p, miR-32-5p e miR-96-5p) foi feita por RT-qPCR, tendo como referência endógena o miR-426-3p. Resultados – A análise de dados demonstrou que o EMFCP possui a capacidade de modular a expressão de miRNAs, estando esta associada à diminuição da expressão do miR-486-3p, miR-34a-5p, miR-210-5p, miR-32-5p e miR-96-5p, reguladores da HbF. Conclusão – O presente estudo sugere que o EMFCP possui potencial indutor da HbF através da modulação de miRNAs reguladores, constituindo assim uma potencial abordagem eficaz na terapêutica das β-hemoglobinopatias.
ABSTRACT Introduction – Hemoglobinopathies constitute one of the most prevalent groups of monogenic diseases worldwide. Currently, one of the available treatments consists of the pharmacological induction of fetal hemoglobin (HbF) using various chemical compounds, the most common one being hydroxyurea (HU). However, its high cost in developing countries and its poor safety profile limit its use. Therefore, it is essential to discover new HbF-inducing compounds with fewer side effects and that are easily accessible, such as natural compounds (e.g., Carica papaya L. leaf extract). Objective – To evaluate the effect of K562 cells’ (an immortalized human myeloid leukemia cell line) exposure to methanolic extracts of Carica papaya L. leaves (EMFCP) on the expression of miRNAs involved in HbF regulation. Methods – K562 cells were exposed for 24 hours to EMFCP (0.5, 50, and 100μg/mL) and HU (25μg/mL). The expression of miRNAs involved in HbF regulation (miR-486-3p, miR-34a-5p, miR-210-5p, miR-32-5p, and miR-96-5p) was analyzed by RT-qPCR, using miR-426-3p as an endogenous reference. Results – Data analysis demonstrated that EMFCP modulates miRNA expression levels, as confirmed by the observation of decreased expression levels of miR-486-3p, miR-34a-5p, miR-210-5p, miR-32-5p, and miR-96-5p, which are HbF regulators. Conclusion – This study suggests that EMFCP has the potential to induce HbF expression through the modulation of regulatory miRNAs, thus constituting a potentially effective approach in the treatment of β-hemoglobinopathies.
ABSTRACT Introduction – Hemoglobinopathies constitute one of the most prevalent groups of monogenic diseases worldwide. Currently, one of the available treatments consists of the pharmacological induction of fetal hemoglobin (HbF) using various chemical compounds, the most common one being hydroxyurea (HU). However, its high cost in developing countries and its poor safety profile limit its use. Therefore, it is essential to discover new HbF-inducing compounds with fewer side effects and that are easily accessible, such as natural compounds (e.g., Carica papaya L. leaf extract). Objective – To evaluate the effect of K562 cells’ (an immortalized human myeloid leukemia cell line) exposure to methanolic extracts of Carica papaya L. leaves (EMFCP) on the expression of miRNAs involved in HbF regulation. Methods – K562 cells were exposed for 24 hours to EMFCP (0.5, 50, and 100μg/mL) and HU (25μg/mL). The expression of miRNAs involved in HbF regulation (miR-486-3p, miR-34a-5p, miR-210-5p, miR-32-5p, and miR-96-5p) was analyzed by RT-qPCR, using miR-426-3p as an endogenous reference. Results – Data analysis demonstrated that EMFCP modulates miRNA expression levels, as confirmed by the observation of decreased expression levels of miR-486-3p, miR-34a-5p, miR-210-5p, miR-32-5p, and miR-96-5p, which are HbF regulators. Conclusion – This study suggests that EMFCP has the potential to induce HbF expression through the modulation of regulatory miRNAs, thus constituting a potentially effective approach in the treatment of β-hemoglobinopathies.
Descrição
Os autores reconhecem o apoio do H&TRC – Centro de Investigação em Saúde e Tecnologia, ESSL – Escola Superior de Saúde de Lisboa, Instituto Politécnico de Lisboa (apoio FCT/MCTES UIDB/05608/2020 e UIDP/05608/2020). Os autores agradecem a gentileza do Sr. Fernando Nunes por colher as folhas de C. papaya L. em Faro, Algarve, Portugal.
Palavras-chave
β-hemoglobinopatias Carica papaya miRNAs Hemoglobina fetal β-hemoglobinopathies Fetal hemoglobin FCT_UIDB/05608/2020 FCT_UIDP/05608/2020
Contexto Educativo
Citação
Ribeiro E, Canteiro B, Ginete C, Gomes M, Brito M, Gomes AQ, Silva C. Modulação da expressão de microRNAs em células humanas K562 induzida por extratos de Carica papaya. Saúde & Tecnologia. 2025;(31):e959. Online first.
Editora
Escola Superior de Tecnologia da Saúde de Lisboa (Instituto Politécnico de Lisboa)