A review of currently identified small molecule modulators of microRNA function

Meter, Emile N. Van; Onyango, Jackline A.; Teske, Kelly A.

doi:10.1016/j.ejmech.2019.112008

Cited by 79 publications

(57 citation statements)

References 174 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One important limitation of the analysis of miRNAs in human CNS tissues, extracellular fluid (ECF) and CSF is that, apart from CNS biopsies, brain tissue samples must be obtained postmortem, and miRNAs have a relatively short post-mortem halflife in both human brain and retina, on the range of about ∼1 to 3 h for a typical 22 nucleotide (nt) single-stranded miRNA (∼45% G + T) in the human neocortical and hippocampal compartments that have been analyzed and for which there is experimental data (Sethi and Lukiw, 2009;Rüegger and Großhans, 2012;Pogue et al, 2014;Tudek et al, 2019). Very few studies have addressed miRNA half-life in vitro or in vivo but currently both miRNA and mRNA decay kinetics have been shown: (i) to follow the same AU-enrichment rules of singlestranded miRNA and mRNA stability that is, the more AUenriched elements (AREs) in the sncRNA, miRNA or mRNA, the shorter the half-life (Sethi and Lukiw, 2009;Rüegger and Großhans, 2012;Clement et al, 2016;Van Meter et al, 2020); (ii) to be stabilized in part by miRNA binding proteins (Zang et al, 2020); (iii) to be further stabilized by circularization (circRNA; Lukiw, 2013a,b;Zhao et al, 2016a,b;Xie et al, 2017;Kondo et al, 2020) and/or (iv) by their inclusion into exosomes or intracellular or extracellular micro-vesicles (Badhwar and Haqqani, 2020;Bitetto and Di Fonzo, 2020;Groot and Lee, 2020;Upadhya et al, 2020). Another indication of the usefulness of post-mortem material for molecular-genetic studies is that nuclei extracted from human brain biopsies or post-mortem brain tissues are able to fully support in vitro run-on transcription for up to ∼3-4 h after which there is a precipitous decline in polymerization activity (Cui et al, 2005;Rüegger and Großhans, 2012;Clement et al, 2016).…”

Section: Overview Of Mirna Abundance In Ad Tissues and Biofluid Compamentioning

confidence: 99%

microRNA-Based Biomarkers in Alzheimer’s Disease (AD)

et al. 2020

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a multifactorial, age-related neurological disease characterized by complex pathophysiological dynamics taking place at multiple biological levels, including molecular, genetic, epigenetic, cellular and large-scale brain networks. These alterations account for multiple pathophysiological mechanisms such as brain protein accumulation, neuroinflammatory/neuro-immune processes, synaptic dysfunction, and neurodegeneration that eventually lead to cognitive and behavioral decline. Alterations in microRNA (miRNA) signaling have been implicated in the epigenetics and molecular genetics of all neurobiological processes associated with AD pathophysiology. These changes encompass altered miRNA abundance, speciation and complexity in anatomical regions of the CNS targeted by the disease, including modified miRNA expression patterns in brain tissues, the systemic circulation, the extracellular fluid (ECF) and the cerebrospinal fluid (CSF). miRNAs have been investigated as candidate biomarkers for AD diagnosis, disease prediction, prognosis and therapeutic purposes because of their involvement in multiple brain signaling pathways in both health and disease. In this review we will: (i) highlight the significantly heterogeneous nature of miRNA expression and complexity in AD tissues and biofluids; (ii) address how information may be extracted from these data to be used as a diagnostic, prognostic and/or screening tools across the entire continuum of AD, from the preclinical stage, through the prodromal, i.e., mild cognitive impairment (MCI) phase all the way to clinically overt dementia; and (iii) consider how specific miRNA expression patterns could be categorized using miRNA reporters that span AD pathophysiological initiation and disease progression.

show abstract

Section: Overview Of Mirna Abundance In Ad Tissues and Biofluid Compamentioning

confidence: 99%

microRNA-Based Biomarkers in Alzheimer’s Disease (AD)

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In the search of SMBs for miRNAs, Drosha/Dicer processing sites or hairpins in pri‐/pre‐miRNAs are attractive targets due to the ability of binders upon interaction to block miRNA processing. Current strategies for the discovery of SMBs of miRNAs include in silico design, high‐throughput experimental screening, and Inforna, which is a hybrid approach of experimental screening and computational prediction [11] . Various SMBs that directly interact with pri‐/pre‐miRNAs have been identified as miRNA inhibitors by using these strategies.…”

Section: Small‐molecule Binders Of Mirnasmentioning

confidence: 99%

Chemical Knockdown of MicroRNA with Small‐Molecule Chimeras

Feng

Yan

2020

ChemBioChem

View full text Add to dashboard Cite

This concept article introduces the emerging area of smallmolecule chimeras (SMCs) for knocking down microRNAs (miRNAs), which are endogenous gene silencers involved in diverse pathological processes. Compared with agents for genetic knockdown, small-molecules hold significant promise in this field due to their ideal pharmacokinetic and pharmacodynamic properties. The SMCs introduced here are hetero-bifunctional molecules comprising small-molecule binders (SMBs) of miRNAs and chemical functionalities that either directly cleave RNAs or recruit ribonucleases to destroy RNAs. Binding of SMBs to miRNAs brings SMCs' chemical functionalities close to the miRNA, eventually causing miRNA degradation. Compared with parent SMBs, SMCs exhibit remarkably enhanced potency and specificity in miRNA inhibition. The development and application of SMCs for miRNAs will be discussed.

show abstract

“…With the development of genetic technology, microRNA (miRNA) has gradually gained attention [ 7 ]. miRNA can be stably expressed in peripheral blood and has become a biological marker of various diseases.…”

Section: Introductionmentioning

confidence: 99%

The Role of miRNA-146a and Proinflammatory Cytokines in Carotid Atherosclerosis

Huang¹,

2020

BioMed Research International

View full text Add to dashboard Cite

The aim of this study was to investigate the expression and significance of miRNA-146a in peripheral blood of patients with carotid atherosclerosis (CAS). Patients with CAS were selected as the stenosis (CAS) group ( n = 180 ). According to the degree of stenosis, they were divided into the mild stenosis group (MS group, n = 64 ), moderate stenosis group (M group, n = 62 cases ), and severe stenosis group (SS group, n = 54 ). According to the plaque type, patients were divided into a stable plaque group (SP group, n = 96 ) and a vulnerable plaque group (VP group, n = 84 ). Patients without CAS represented the normal group ( n = 90 ). The expression levels of miRNA-146a as well as IL-6 and TNF-α in peripheral blood were detected by RT-PCR and ELISA, respectively. The expression levels of miRNA-146a, IL-6, and TNF-α in the CAS group were higher than those in the normal group and positively correlated with the degree of stenosis and plaque vulnerability. The expression levels of miRNA-146a, IL-6, and TNF-α in the stable plaque group were lower than those in the vulnerable plaque group. The area under the curve of miRNA-146a predicting the vulnerability of plaques was significant at 0.641. The expression level of miRNA-146a in the CAS group was positively correlated with IL-6 and TNF-α levels. Our results indicate that miRNA-146a may participate in the occurrence and development of CAS by regulating the expression of IL-6 and TNF-α, which may be potential biomarkers of CAS.

show abstract

A review of currently identified small molecule modulators of microRNA function

Cited by 79 publications

References 174 publications

microRNA-Based Biomarkers in Alzheimer’s Disease (AD)

microRNA-Based Biomarkers in Alzheimer’s Disease (AD)

Chemical Knockdown of MicroRNA with Small‐Molecule Chimeras

The Role of miRNA-146a and Proinflammatory Cytokines in Carotid Atherosclerosis

Contact Info

Product

Resources

About