MicroRNA-4422-5p as a Negative Regulator of Amyloidogenic Secretases: A Potential Biomarker for Alzheimer's Disease

Beta-secretase (BACE1) and gamma-secretase activating protein (GSAP) are pivotal enzymes in the cleavage of amyloid precursor protein (APP). Beta-amyloid (A�) formation is considered one of the main reasons for Alzheimer's disease (AD) pathology. In our preliminary study, a series of microRNAs (miRs) with possible interaction with BACE1 and/or GSAP was selected using computational analysis. Our results showed that miR-4422-5p had a reduced level in the serum of AD patients. In this study, the effect of miR-4422-5p using miR-4422-5p mimic and inhibitor on BACE1 and GSAP were investigated, and a probable novel early diagnostic marker for AD was introduced. The effect of miR-4422-5p interaction with BACE1 and GSAP was evaluated via in vitro experiments using dual-luciferase assays, western blotting, and Immunocytochemistry. Luciferase assay demonstrated that miR-4422-5p mimic suppresses BACE1 and GSAP expression by directly targeting the 3�UTR of BACE1 and GSAP mRNA in HEK293T cells. Also, western blotting and immunocytochemistry confirmed the regulatory role of miR-4422-5p mimic on BACE1 and GSAP genes. miR-4422-5p mimic significantly decreased BACE1 and GSAP protein expression in SH-SY5Y and A549 cells, respectively. Moreover, miR-4422-5p-inhibitor reversed the expression processes in both cell lines. Our data suggest that miR-4422-5p may be an important regulator of both BACE1 and GSAP genes and can represent a novel potential biomarker or therapeutic target in AD. © 2021 IBR

MicroRNA-Based Biomarkers in Lung Cancer: Recent Advances and Potential Applications

Introduction: MicroRNAs (miRNAs) are a group of small noncoding RNAs (ncRNAs) that post-transcriptionally control the expression of genes by binding and degrading their target mRNAs. miRNAs can function as possible tumor suppressors or oncogenes in various cancers. Lately, miRNAs application as a biomarker (prognosis and diagnosis) for different diseases has gained much attention. miRNAs exist in a stable form in several biological materials, including tissue, plasma, and serum. The noninvasive and easy screening of miRNAs in serum, blood, tissue, and other body fluids and acceptable stability make microRNA a noticeable factor as biomarkers in human malignancies. Materials and Methods: In this review, we searched some online databases like Web of Science, Embase, and PubMed to find eligible manuscripts up to the end of 2021. Results: Abnormal expressions of these molecules are associated with the incidence of many illnesses like cancer. Therefore, they are candidates as a molecular tool for noninvasive tumor prognosis and diagnosis. In the current study, we introduce important miRNAs that may be used as prognostic and diagnostic markers in lung cancer patients. Conclusion: We summarized the latest reports about critical miRNAs related to the diagnosis and prognosis in lung patients. © 2023 Bentham Science Publishers.This study was supported by the Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Science, Tabriz, Iran

Beta-Amyloid-Dependent miRNAs as Circulating Biomarkers in Alzheimer�s Disease: a Preliminary Report

MicroRNAs (miRNAs) are considered among the most reliable biomarkers to diagnose and predict Alzheimer�s disease (AD), due to their regulatory nature. The main goal of this study was to evaluate the expression of miR4422 and miR3714, as the main regulators of GSAP and BACE1 expression, in AD patients compared with healthy subjects. Twenty patients with a mild to moderate AD (58�71 years old) and 15 healthy subjects (58�73 years old) participated in this study. The expression levels of miR4422 and miR3714 as the target genes and 5S rRNA and miRlet7a-5p as the reference genes were measured in the two groups. To compare the expression between the case and the control groups, the t test or the Wilcoxon test was used, based on the data distribution patterns. The efficiencies of amplification of the miR4422, miR3714, 5S rRNA, and miRlet7a-5p genes all were in the acceptable range. The mean miR4422-5S rRNA dCt value was significantly different between the two groups (p = 0.018). The relative fold change of the expression was 0.43. The mean miR4422-miRlet7a-5p dCt value (p = 0.41), the mean miR3714-5S rRNA dCt value (p = 0.10), and the mean miR3714-miRlet7a-5p dCt value (p = 0.063) were not significantly different between the two groups. We indicated that miR4422 could be a reliable biomarker for Alzheimer�s diagnosis. It seems that the reduced expression of miR4422 that targets GSAP and BACE1 expression can lead to an increase in the formation of Aβ plaque. © 2020, Springer Science+Business Media, LLC, part of Springer Nature

AN OVERVIEW OF THE HISTORY, APPLICATIONS, ADVANTAGES, DISADVANTAGES AND PROSPECTS OF GENE THERAPY

Gene therapy has become a significant issue in science-related news. The principal concept of gene therapy is an experimental technique that uses genes to treat or prevent disease. Although gene therapy was originally conceived as a way to treat life-threatening disorders (inborn defects, cancers) refractory to conventional treatment, it is now considered for many non life-threatening conditions, such as those adversely impacting a patient's quality of life. An extensive range of efficacious vectors, delivery techniques, and approaches for developing gene-based interventions for diseases have evolved in the last decade. The lack of suitable treatment has become a rational basis for extending the scope of gene therapy. The aim of this review is to investigate the general methods by which genes are transferred and to give an overview to clinical applications. Maximizing the potential benefits of gene therapy requires efficient and sustained therapeutic gene expression in target cells, low toxicity, and a high safety profile. Gene therapy has made substantial progress albeit much slower than was initially predicted. This review also describes the basic science associated with many gene therapy vectors and the present progress of gene therapy carried out for various surface disorders and diseases. The conclusion is that, with increased pathobiological understanding and biotechnological improvements, gene therapy will become a standard part of clinical practice

Terminalia Catappa Extract (TCE) Reduces Proliferation Of Lung And Breast Cancer Cell By Modulating miR-21 And miR-34a Expressions

After cardiovascular illness, cancer is the one of the main and second cause of death in the worldwide. Despite significant advances in this field, low survival, drug resistance, and side effects of chemotherapy remain an unsolved problem. Due to the high mortality rate among cancer patients, finding the new substance to treatment with low side effects is important. Previous studies have been informed that positive effects of herbal medicines on cancer patients, which are very efficient in the treatment of cancer. Methods: In this study, the antitumor effect of ethanolic Terminalia catappa leaf extract (TCE) on MCF-7, MDA-231, and A549 cell lines was examined. For this reason, the effects of TCE on cell migration, gene expression, and growth were investigated by scratch, test, real-time PCR (qPCR) qPCR, and MTT tests respectively. Results: As a reported by the MTT outcomes, TCE significantly decreased the viability of A549, MCF-7, and MDA-231 cells (P < 0.05). Moreover, genes expression patterns that are related to proliferation (miR-21, miR-34a), migration (MMP-13, Vimentin), and apoptosis (Cas-3, Cas-8, Cas-9, Bcl-2, Bax) also have changed significantly after treatment with TCE. Also, in the A549 cell line, Bax (p value: 0.029), Cas-9 (p value: 0.00023), miR-34a (p value: 0.031), Bcl-2 (p value: 0.0076), MMP-13 (p value: 0.041), Cas-3 (p value: 0.00051) and in MCF-7 cell line Bax (p value: 0.0004), Cas-3 (p value: 0.0003), Cas-9(p value: 0.037), miR-34a (p value: 0.005), Bcl-2(pvalue:0.0007), mir-21(p value:0.016), MMP-13(p value: 0.011) and in MDA-231 cell line Bax(p value<0.0001), Cas-3(p value: 0.003), Cas-9(p value: 0.0004). mir-34a (p value:0.0019), Bcl-2(p value:0.0023), MMP-13(p value: 0.032) have significantly changed compare to control group. Conclusion: The outcomes of this research determined that T. Catappa might be a potential source of antitumor compounds and could be a candidate for further research. © 2021. All Rights Reserved.This study was supported by a grant from research deputy of Department of Tuberculosis and Lung Diseases Research Center, University Tabriz University of Medical Sciences, Tabriz, Iran