ABSTRACT
OBJECTIVE: The present study investigated the role of miR-181a as a small non-coding RNA molecule in acute myeloid leukemia (AML) pathogenesis and reflected on the effects of Sulforaphane (SFN) on AML progression. MATERIALS AND METHODS: This experimental study had two parts. In vivo study, the miR-181a levels was measured in patients with symptoms of AML and compared to healthy controls (HCs) to investigate its role in AML pathogenesis. Afterward, an in vitro study was performed to examine the effects of SFN on the growth, apoptosis and proliferation rate of AML cell lines. Finally, the effect of SFN on miR-181a was evaluated as a major miRNA involved in hematopoiesis. RESULTS: The results of this study showed an increasing trend (2.9-fold, P=0.0019) in miR-181a expression levels in AML patients as compared with HCs. The data associated with MTT assay and flow cytometry (FCM) additionally demonstrated the anti-proliferative effects of SFN against AML cell lines, with a reduction in miR-181a levels. As well, no significant difference was noted between 24 hours and 48 hours treatments by SFN. It was deduced that modulation of miR-181a expression levels could be one of the mechanisms associated with the anti-proliferative effects of SFN against AML. CONCLUSION: MiR-181a levels contribute to AML pathogenesis and thus they can be considered as a strategy in controlling AML progression in patients. Accordingly, SFN can arrest cell proliferation and induce apoptosis in AML cell lines through retardation expression of miR-181a and affecting miR-181a pathway, which already clarified its role in the differentiation of hematopoietic stem cells and indicates another mode of anti-cancer action of sulforaphane.
ABSTRACT
[This corrects the article DOI: 10.18502/ijrm.v19i6.9376.].
ABSTRACT
BACKGROUND: Oxidative stress is caused by the imbalance occurring between the creation and clearance of the reactive oxygen species (ROS), which is responsible for 30-40% of male infertility. The positive impact of phoenix dactylifera pollen (Date palm pollen, DPP) on the improvement of sperm parameters has been well documented in animal models. OBJECTIVE: For evaluating the effect(s) of DPP on sperm parameters, ROS levels, expression of antioxidant genes, and activity of antioxidant enzymes of infertile men. MATERIALS AND METHODS: In this controlled clinical trial, a total of 60 male case with infertility and 20 normospermic fertile men were recruited. Before and after the treatment with DPP, the case were administered 400 mg/kg of gelatinous capsules daily for 30 consecutive days and semen samples were taken. Quantitative real-time polymerase chain reaction was applied for the evaluation of the mRNA expression levels of Nuclear factor erythroid 2-related factor 2(NRF2), superoxide dismutase (SOD2), glutathione peroxidase 4(GPX4), and catalase (CAT) genes. RESULTS: The mRNA expression levels of NRF2, SOD2, GPX4, and CAT (p < 0.05 for all) and significantly increased after treatment with DPP. The increased expressions of all antioxidant genes and enzymes significantly correlated with improvement in semen parameters including count (p = 0.01), motility (p = 0.05), and morphology (p = 0.01) of sperm. A significant correlation between the alteration of SOD2 gene expression and SOD activity, GPX4 and GPX, and CAT were also observed (p = 0.05). CONCLUSION: DPP can increase the expressions of NRF2, GPX4, SOD2, and CAT genes and also improve the semen quality in infertile men.
ABSTRACT
INTRODUCTION: The most common type of leukemia is acute myeloid leukemia (AML) with the lowest survival rate among all of the leukemias particularly in adults. The evidence has shown that dysregulation of miRNA expression is associated with AML. Therefore, the aim of this systematic review was to clarify the role of miR-181a expression in AML. METHODS AND ANALYSIS: In the present study, observational studies of the roles of miR-181a expression in patients with AML will be included. Standards and indicators test should be performed for all patients. We will search PubMed, SCOPUS and ISI Web of Science with no restriction of language. The outcomes will be reviewed for association between miR-181a level and AML progression and the strength of this relationship with AML will be investigated. Selection of articles and data extraction will be performed by two independent reviewers. STROBE will be used for assessment of study quality. Publication bias and data synthesis will be an assessment by funnel plots and Beggs and Egger's tests using Stata software V.12.1. ETHICS AND DISSEMINATION: There are no ethical issues. TRIAL REGISTRATION NUMBER: This systematic review protocol is registered in the PROSPERO (International Prospective Register of Systematic Reviews), and registration number CRD42016040080.
ABSTRACT
The expression of microRNA in eukaryotic cells is subject to tightly regulated processing. The altered expression of microRNAs in a number of cancers suggests their contribution to disease pathogenesis, where processing pathways may be involved in disease pathogenesis. In the present study, we evaluated changes in the profile of two main components of microRNA biogenesis, AGO2 and DICER, and assessed their correlation with disease progression in childhood acute lymphoblastic leukaemia (ALL). To achieve this aim, 25 patients afflicted with ALL were included in the study along with 25 healthy subjects as control. The expression level of AGO2 and DICER was evaluated by real-time PCR. The results revealed an increase in the expression of DICER and a decrease in AGO2 in patients. The correlation between the alteration levels of these genes with pathologic events was also studied. This increase or decrease proved to be directly correlated with the progression of the disease particularly in L1 to L2. According to the obtained results, it can be deduced that dysregulation in transcription of DICER and AGO2, involved in the formation of mature microRNAs in cytoplasm of ALL cancer cells, is a part of the pathological molecular mechanism implicated in the exacerbation of this malignancy. Therefore, the genes involved in microRNAs biogenesis that have been studied here could be considered as candidate prognostic markers especially in childhood ALL which will help towards a better understanding of the molecular basis of ALL.
Subject(s)
Argonaute Proteins/metabolism , B-Lymphocytes/cytology , Cell Lineage/immunology , DEAD-box RNA Helicases/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Ribonuclease III/metabolism , Adolescent , Child , Child, Preschool , Disease Progression , Female , Humans , Male , MicroRNAs/genetics , Real-Time Polymerase Chain Reaction/methodsABSTRACT
Acute myeloid leukemia (AML) has the highest rate of mortality among the leukemias. Disruption in miRNAs level is involved in the pathogenesis of the disease. The miR-155 has a role in primary differentiation of myeloid progenitor. Meanwhile, there is little knowledge about the effects of sulforaphane against leukemia. The present study tried to evaluate pathologic effect of miR-155 in patients in various subgroups of AML, and then pioneered in assessing miR-155 levels by the effect of sulforaphane in different AML cell lines. The miR-155 level was significantly higher in patients with AML compared to the controls. Interestingly, the increase in miR-155 was converged with raising the subtype of AML (from M1 to M5). The miR-155 levels increased by 1.2 times in patients with M1, but this increase reached 2.5 times in the patients in the M5 subgroup. Sulforaphane reduced the number of live cells and increased the mortality rate of AML cells particularly by induction of apoptosis. However, the anti-proliferative effect of this agent was more dominant and could dose-dependently lessen miR-155 levels in myeloid leukemia cells. More or less, about 80% reduction in miR-155 expression was almost observed after 48 h treatment with 60 µM sulforaphane in all four studied cell lines. The obtained results indicated that miR-155 might function as an oncomir in AML and can potentially be considered as a prognosis biomarker for AML. The anti-cancer effects of sulforaphane can be correlated with reduction of miR-155 levels. These findings suggested that sulforaphane could induce more differentiation in myeloid progenitor cells through controlling the miR-155, thereby mitigating the progress of AML.
