MicroRNAs are the major class of small non‐coding RNAs, evolutionary conserved post‐transcriptional regulators of gene expression. Since their discovery in 1993, they have been implicated as master regulators in numerous cellular processes. MicroRNA (miRNA)s regulate gene expression by attenuation and/or mRNA degradation and are commonly associated with cell development, differentiation, and homeostasis. Extensive research in past two decades has provided new insights into the potential implications of miRNA in the onset, progression, and therapeutic nature of miRNAs in disease manifestation. Owing to the novel discoveries, “miRNAs” would probably pave a new direction in therapeutic research. However, “micro” in length miRNAs have attracted considerable attention in numerous other fields. Understanding the functionality of miRNAs, in this review article, we discussed the mechanistic role of miRNAs in human diseases and have outlined most of the recent published work in clinical therapeutics. We have constructed different network models for miRNA and its targets which made us understand their interrelationship and association with diseases. Future research would surely overcome challenges and would introduce new strategies for the utility of miRNAs in a broader setting.
Hydroxyurea (HU) is found to be beneficial in sickle cell anaemia (SCA) patients, due to its ability to increase foetal haemoglobin (HbF), however, patients show a variable response. Differences in HbF levels are attributed to many factors; but, the role of miRNA in HbF regulation is sparsely investigated. In this study, we evaluated the effect of miRNA expression on HbF induction in relation to hydroxyurea therapy in 30 normal controls, 30 SCA patients at baseline, 20 patients after 3 and 6 months of hydroxyurea (HU) therapy. HbF levels were measured by HPLC. Total RNA and miRNA were extracted from CD71+ erythroid cells and the expression was determined using Taqman probes. The mean HbF level increased 7.54 ± 2.44 fold, after 3 months of HU therapy. After the HU therapy 8 miRNAs were significantly up-regulated while 2 were down-regulated. The increase in miR-210, miR16-1, and miR-29a expression and decrease in miR-96 expression were strongly associated with the HU mediated HbF induction. Post HU therapy, decreased miR-96 expression negatively correlate with HbF and γ-globin gene while increased expression of miR-210, miR-16-1 and miR-29a post HU therapy positively corelate with HbF and γ-globin gene. Thus, suggest that miR-210, miR-16-1 and miR-29a are positive regulator of γ-globin gene and miR-96 is negative regulator of γ-globin gene. The study suggests the role of miR-210, miR16-1, miR-29a, and miR-96 in γ-globin gene regulation leading to HbF induction. Identification of the relevant protein targets might be useful for understanding the HU mediated HbF induction.
Background:Hydroxyurea (HU) is found to be beneficial in Sickle cell Anaemia (SCA) patients, due to its ability to increase foetal haemoglobin (HbF), however, patients show a variable response. Differences in HbF levels are attributed to many factors; but, the role of miRNA in HbF regulation is sparsely investigated.Materials and Methods:In this study, we evaluated the effect of miRNA expression on HbF induction in relation to hydroxyurea therapy in 30 normal controls, 30 SCA patients at baseline, 20 patients after 3 and 6 months of hydroxyurea (HU) therapy. HbF levels were measured by HPLC. Total RNA and miRNA were extracted from CD71+ erythroid cells and the expression was determined using Taqman probes. Results:The mean HbF level increased 7.54 ±2.44 fold, after 3 months of HU therapy. After the HU therapy 8 miRNAs were significantly up-regulated while 2 were down-regulated. The increase in miR-210, miR16-1, and miR-29a expression and decrease in miR-96 expression were strongly associated with the HU mediated HbF induction. Post HU therapy, decreased miR-96 expression was observed; which might be due to interference of miR-96 binding to g-globin mRNA by HU, facilitating HbF expression. The miR-210 expression was enhanced in association with erythroid differentiation and induction to HbF production. Conclusions:The study suggests the role of miR-210, miR16-1, miR-29a, and miR-96 in g-globin gene regulation leading to HbF induction. Identification of the relevant protein targets might be useful for understanding the HU mediated HbF induction.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.