scholarly journals The Role of Exo-miRNAs in Cancer: A Focus on Therapeutic and Diagnostic Applications

2019 ◽  
Vol 20 (19) ◽  
pp. 4687 ◽  
Author(s):  
Francesco Ingenito ◽  
Giuseppina Roscigno ◽  
Alessandra Affinito ◽  
Silvia Nuzzo ◽  
Iolanda Scognamiglio ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Biological Fluids ◽  
Translational Repression ◽  
Regulate Gene Expression ◽  
Physiological Processes ◽  
Non Coding Rna ◽  
Diagnostic Applications ◽  
Tumoral Cells ◽  
Potential Cancer

Exosomes are extracellular vesicles released into biological fluids where they act as carriers of various molecules, including proteins, lipids, and RNAs, between cells, modulating or perturbing specific physiological processes. Recently, it has been suggested that tumoral cells release excessive amounts of exosomes that, through their cargo, promote tumor progression, stimulating growth, angiogenesis, metastasis, insensitivity to chemotherapy, and immune evasion. Increasing evidence highlights exosomal microRNAs (exo-miRNAs) as important players in tumorigenesis. MicroRNA (miRNA) are a class of small non-coding RNA able to regulate gene expression, targeting multiple mRNAs and inducing translational repression and/or mRNA degradation. Exo-miRNAs are highly stable and easily detectable in biological fluids, and for these reasons, miRNAs are potential cancer biomarkers useful diagnostically and prognostically. Furthermore, since exosomes are natural delivery systems between cells, they can be appropriately modified to carry therapeutic miRNAs to specific recipient cells. Here we summarize the main functions of exo-miRNAs and their possible role for diagnostic and therapeutic applications.

scholarly journals MicroRNAs: The Role in Autoimmune Inflammation

Acta Naturae ◽  
2016 ◽  
Vol 8 (1) ◽  
pp. 21-33 ◽  
Author(s):  
N. M. Baulina ◽  
O. G. Kulakova ◽  
O. O. Favorova
Keyword(s):  
Transcriptional Level ◽  
Regulate Gene Expression ◽  
Rna Molecules ◽  
Autoimmune Inflammation ◽  
Non Coding Rna ◽  
Human Genes ◽  
The Central Nervous System ◽  
Significant Disease ◽  
Antibody Secretion

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level through base-pairing predominantly with a 3-untranslated region of target mRNA, followed by mRNA degradation or translational repression. Totally, miRNAs change, through a complex regulatory network, the expression of more than 60% of human genes. MiRNAs are key regulators of the immune response that affect maturation, proliferation, differentiation, and activation of immune cells, as well as antibody secretion and release of inflammatory mediators. Disruption of this regulation may lead to the development of various pathological conditions, including autoimmune inflammation. This review summarizes the data on biogenesis and the mechanisms of miRNA action. We discuss the role of miRNAs in the development and the action of the immune system, as well as in the development of an autoimmune inflammatory response. Special attention is given to the role of miRNAs in the autoimmune inflammation in multiple sclerosis, which is a serious socially significant disease of the central nervous system. Currently, a lot of research is focused on this problem.

scholarly journals The Regulatory Role of MicroRNAs in Breast Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4940 ◽  
Author(s):  
Hui-Yi Loh ◽  
Brendan P. Norman ◽  
Kok-Song Lai ◽  
Nik Mohd Afizan Nik Abd. Rahman ◽  
Noorjahan Banu Mohamed Alitheen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Recurrence ◽  
Messenger Rnas ◽  
Aberrant Expression ◽  
Regulate Gene Expression ◽  
Rna Molecules ◽  
Current State ◽  
Non Coding Rna ◽  
State Of Research

MicroRNAs (miRNAs) are small non-coding RNA molecules which function as critical post-transcriptional gene regulators of various biological functions. Generally, miRNAs negatively regulate gene expression by binding to their selective messenger RNAs (mRNAs), thereby leading to either mRNA degradation or translational repression, depending on the degree of complementarity with target mRNA sequences. Aberrant expression of these miRNAs has been linked etiologically with various human diseases including breast cancer. Different cellular pathways of breast cancer development such as cell proliferation, apoptotic response, metastasis, cancer recurrence and chemoresistance are regulated by either the oncogenic miRNA (oncomiR) or tumor suppressor miRNA (tsmiR). In this review, we highlight the current state of research into miRNA involved in breast cancer, with particular attention to articles published between the years 2000 to 2019, using detailed searches of the databases PubMed, Google Scholar, and Scopus. The post-transcriptional gene regulatory roles of various dysregulated miRNAs in breast cancer and their potential as therapeutic targets are also discussed.

scholarly journals Obesity, leptin, and deregulation of microRNA in lipid metabolisms: their contribution to breast cancer prognosis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Kartika W. Taroeno-Hariadi ◽  
Mardiah S. Hardianti ◽  
Hemi Sinorita ◽  
Teguh Aryandono
Keyword(s):  
Breast Cancer ◽  
Metabolic Syndrome ◽  
Target Genes ◽  
Breast Cancer Prognosis ◽  
Cancer Prognosis ◽  
Regulate Gene Expression ◽  
Non Coding Rna ◽  
Post Menopause ◽  
Points Of View

AbstractObesity and Metabolic Syndrome have been associated with cardiovascular, diabetes and cancer incidence. Obesity is a state of inflammation. There are cross-talks between adipocyte, adipokines, pro-inflammatory cytokines, insulin, leptin, and other growth factors to initiate signals for proliferation, anti-apoptosis, and angiogenesis. Those networks lead to cancer initiation, promotion, progression, and metastasis. Post menopause women with breast cancer commonly have overweight, obesity, and metabolic syndrome, which are previously reported as conditions to be associated with breast cancer prognosis. MicroRNAs (miRNAs), small non-coding RNA that regulate gene expression, are known to play important roles either in metabolic or carcinogenesis process in patients with breast cancer. Some miRNAs expressions are deregulated in persons either with obesity, breast cancer, or breast cancer with co-morbid obesity. This literature review aimed at reviewing recent publications on the role of obesity, leptin, and microRNA deregulation in adverse prognosis of breast cancer. Understanding the influence of deregulated miRNAs and their target genes in patients with breast cancer and obesity will direct more studies to explore the potential prognostic role of obesity in breast cancer from epigenetic points of view.

The miRNA-kallikrein interaction: a mosaic of epigenetic regulation in cancer

2018 ◽  
Vol 399 (9) ◽  
pp. 973-982 ◽  
Author(s):  
Ashley Di Meo ◽  
Cong Wang ◽  
Yufeng Cheng ◽  
Eleftherios P. Diamandis ◽  
George M. Yousef
Keyword(s):  
Epigenetic Regulation ◽  
Serine Proteases ◽  
Untranslated Region ◽  
Regulate Gene Expression ◽  
Mrna Targets ◽  
Downstream Effectors ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation ◽  
Potential Cancer

AbstractThe kallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases with trypsin- and chymotrypsin-like activities. Dysregulated expression and/or aberrant activation of KLKs has been linked to various pathophysiological processes, including cancer. Many KLKs have been identified as potential cancer biomarkers. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression by pairing to the 3′ untranslated region (UTR) of complimentary mRNA targets. miRNAs are dysregulated in many cancers, including prostate, kidney and ovarian cancers. Several studies have shown that miRNAs are involved in the post-transcriptional regulation of KLKs. However, recent evidence suggests that miRNAs can also act as downstream effectors of KLKs. In this review, we provide an update on the epigenetic regulation of KLKs by miRNAs. We also present recent experimental evidence that supports the regulatory role of KLKs on miRNA networks. The potential diagnostic and therapeutic applications of miRNA-kallikrein interactions are also discussed.

scholarly journals Adding a “Notch” to Cardiovascular Disease Therapeutics: A MicroRNA-Based Approach

2021 ◽  
Vol 9 ◽  
Author(s):  
Luisa Marracino ◽  
Francesca Fortini ◽  
Esmaa Bouhamida ◽  
Francesca Camponogara ◽  
Paolo Severi ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Molecular Mechanisms ◽  
Notch Pathway ◽  
Biological Processes ◽  
Rna Sequences ◽  
Regulate Gene Expression ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
Mirnas Expression

Dysregulation of the Notch pathway is implicated in the pathophysiology of cardiovascular diseases (CVDs), but, as of today, therapies based on the re-establishing the physiological levels of Notch in the heart and vessels are not available. A possible reason is the context-dependent role of Notch in the cardiovascular system, which would require a finely tuned, cell-specific approach. MicroRNAs (miRNAs) are short functional endogenous, non-coding RNA sequences able to regulate gene expression at post-transcriptional levels influencing most, if not all, biological processes. Dysregulation of miRNAs expression is implicated in the molecular mechanisms underlying many CVDs. Notch is regulated and regulates a large number of miRNAs expressed in the cardiovascular system and, thus, targeting these miRNAs could represent an avenue to be explored to target Notch for CVDs. In this Review, we provide an overview of both established and potential, based on evidence in other pathologies, crosstalks between miRNAs and Notch in cellular processes underlying atherosclerosis, myocardial ischemia, heart failure, calcification of aortic valve, and arrhythmias. We also discuss the potential advantages, as well as the challenges, of using miRNAs for a Notch-based approach for the diagnosis and treatment of the most common CVDs.

Evaluating the effect of siRNA on SOX2OT expression in the human neuron-committed teratocarcinoma NT2 cell line

2020 ◽  
Vol 28 (4) ◽  
pp. 299-303
Author(s):  
Zahra Sadeghi ◽  
Fateme Dodange ◽  
Parichehr Maleki ◽  
Mohadeseh Zarei ◽  
Mohammad Taheri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Concomitant Increase ◽  
Regulate Gene Expression ◽  
Non Coding Rna ◽  
Regulate Gene

Non-coding RNA elongated (lncRNAs) have recently attracted as molecules that regulate gene expression of the pluripotent properties (pluripotency) of stem cells. Recently our colleagues examined the role of one of these RNAs called SOX2OT in esophageal squamous cell carcinoma, and found a concomitant increase in its expression with some regulatory genes of cell proliferation. In the present study, using the design of suitable primers from SOX2OT gene, we investigated the effect of siRNA on expression of SOX2OT.

scholarly journals miRNAs as Influencers of Cell–Cell Communication in Tumor Microenvironment

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 220 ◽  
Author(s):  
Ilaria Conti ◽  
Gabriele Varano ◽  
Carolina Simioni ◽  
Ilaria Laface ◽  
Daniela Milani ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cell Communication ◽  
Altered Expression ◽  
Regulate Gene Expression ◽  
Small Noncoding Rnas ◽  
Physiological Processes ◽  
Extracellular Mirnas ◽  
Obesity And Cancer ◽  
Posttranscriptional Level

microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level, inducing the degradation of the target mRNA or translational repression. MiRNAs are involved in the control of a multiplicity of biological processes, and their absence or altered expression has been associated with a variety of human diseases, including cancer. Recently, extracellular miRNAs (ECmiRNAs) have been described as mediators of intercellular communication in multiple contexts, including tumor microenvironment. Cancer cells cooperate with stromal cells and elements of the extracellular matrix (ECM) to establish a comfortable niche to grow, to evade the immune system, and to expand. Within the tumor microenvironment, cells release ECmiRNAs and other factors in order to influence and hijack the physiological processes of surrounding cells, fostering tumor progression. Here, we discuss the role of miRNAs in the pathogenesis of multicomplex diseases, such as Alzheimer’s disease, obesity, and cancer, focusing on the contribution of both intracellular miRNAs, and of released ECmiRNAs in the establishment and development of cancer niche. We also review growing evidence suggesting the use of miRNAs as novel targets or potential tools for therapeutic applications.

scholarly journals A novel tsRNA-16902 regulating the adipogenicdifferentiation of human bone marrow mesenchymal stem cells

2020 ◽  
Author(s):  
Tao Wang ◽  
Jun Mei ◽  
Xing-nuan Li ◽  
Xiao-yuan Xu ◽  
Bai-cheng Ma ◽  
...  
Keyword(s):  
Retinoic Acid Receptor ◽  
Adipogenic Differentiation ◽  
Marker Gene ◽  
Luciferase Reporter ◽  
Bioinformatics Analyses ◽  
Physiological Processes ◽  
Non Coding Rna ◽  
Marrow Mesenchymal Stem Cells ◽  
Reporter Assays

Abstract Background: Transfer RNA-derived small RNAs (tsRNAs) are a recently discovered form of non-coding RNA capable of regulating myriad physiological processes. The role of tsRNAs in hMSC adipogenic differentiation, however, remains incompletely understood. The purpose of this study was to identify the novel tsRNA-16902 as a regulator of hMSC adipogenic differentiation.Methods: In this study we conducted transcriptomic sequencing of hMSCs after inducing their adipogenic differentiation, and we were thereby able to clarify the molecular mechanism underlying the role of tsRNA-16902 in this context via a series of molecular biology methods. Results: When we knocked down tsRNA-16902 expression, this impaired hMSC adipogenic differentiation and associated marker gene expression. Bioinformatics analyses further revealed tsRNA-16902 to target retinoic acid receptor γ (RARγ). Luciferase reporter assays also confirmed the ability of tsRNA-16902 to bind to the RARγ 3’-untranslated region. Consistent with this, RARγ overexpression led to impaired hMSC adipogenesis. Further analyses additionally revealed that Smad2/3 phosphorylation as increased in cells that either overexpressed RARγ or in which tsRNA-16902 had been knocked down. We also assessed the adipogenic differentiation of hMSCs in which tsRNA-16902 was knocked down and at the same time a Smad2/3 inhibitor was added to disrupt Smad2/3 phosphorylation. The adipogenic differentiation of hMSCs in which tsRNA-16902 was knocked down was further enhanced upon the addition of a Smad2/3 signaling inhibitor relative to tsRNA-16902 knockdown alone.Conclusions: Through a comprehensive profiling analysis of tsRNAs that were differentially expressed in the context of hMSC adipogenic differentiation, we were able to identify tsRNA-16902 as a previously uncharacterized regulator of adipogenesis. tsRNA-16902 is able to regulate hMSC adipogenic differentiation by targeting RARγ via the Smad2/3 signaling pathway. Together our results may thus highlight novel strategies of value for treating obesity.

scholarly journals The Role of Exosomes and Their Applications in Cancer

2021 ◽  
Vol 22 (22) ◽  
pp. 12204
Author(s):  
Yuju Zhou ◽  
Ying Zhang ◽  
Huan Gong ◽  
Siqi Luo ◽  
Yan Cui
Keyword(s):  
High Efficiency ◽  
Biological Fluids ◽  
Cell Types ◽  
Therapeutic Delivery ◽  
Diagnosis And Prognosis ◽  
Multiple Cell ◽  
Diagnostic Applications ◽  
Different Sources ◽  
Target Cancer

Exosomes are very small extracellular vesicles secreted by multiple cell types and are extensively distributed in various biological fluids. Recent research indicated that exosomes can participate in regulating the tumor microenvironment and impacting tumor proliferation and progression. Due to the extensive enrollment in cancer development, exosomes have become a focus of the search for a new therapeutic method for cancer. Exosomes can be utilized for the therapeutic delivery of small molecules, proteins and RNAs to target cancer cells with a high efficiency. Exosome-carried proteins, lipids and nucleic acids are being tested as promising biomarkers for cancer diagnosis and prognosis, even as potential treatment targets for cancer. Moreover, different sources of exosomes exhibit multiple performances in cancer applications. In this review, we elaborate on the specific mechanism by which exosomes affect the communication between tumors and the microenvironment and state the therapeutic and diagnostic applications of exosomes in cancers.

scholarly journals The Role of MicroRNAs in Antiarrhythmic Therapy for Atrial Fibrillation

2015 ◽  
Vol 4 (3) ◽  
pp. 146 ◽  
Author(s):  
Sebastian Clauss ◽  
Moritz F Sinner ◽  
Stefan Kääb ◽  
Reza Wakili ◽  
◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Molecular Mechanisms ◽  
Calcium Handling ◽  
Ectopic Activity ◽  
Atrial Fibrosis ◽  
Key Factors ◽  
Regulate Gene Expression ◽  
Non Coding Rna ◽  
Rna Fragments

Atrial fibrillation (AF) is the most common arrhythmia worldwide and has an enormous impact on our healthcare system as it is a major contributor of morbidity and mortality. Although there are several therapeutic options available, treatment of AF still remains challenging. AF pathophysiology is complex and still incompletely understood. In general, our understanding of AF is based on two mechanistic paradigms as functional hallmarks of AF: ectopic activity and reentry. Both ectopic activity and reentry are the result of remodelling processes. Functional and/or expressional changes in ion channels, connexins or calcium-handling proteins are important factors in electrical remodelling, whereas signalling processes leading to atrial dilatation and atrial fibrosis are key factors of structural remodelling. In recent years, new intriguing key players in AF pathophysiology have been identified: microRNAs (miRNAs). MiRNAs are short, non-coding RNA fragments that can regulate gene expression and have been demonstrated as important modifiers in signalling cascades leading to electrical and structural remodelling. In this article we review the miRNA-mediated molecular mechanisms underlying AF with special emphasis on the perspective of miRNAs as potential therapeutic targets for AF treatment.

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