Abstract:
:MicroRNAs (miRNAs) are small RNAs repressing gene expression. They contribute to many physiological processes and pathologies. Consequently, strategies for manipulation of the miRNA pathway are of interest as they could provide tools for experimental or therapeutic interventions. One of such tools could be small chemical compounds identified through high-throughput screening (HTS) with reporter assays. While a number of chemical compounds have been identified in such high-throughput screens, their application potential remains elusive. Here, we report our experience with cell-based HTS of a library of 12,816 chemical compounds to identify miRNA pathway modulators. We used human HeLa and mouse NIH 3T3 cell lines with stably integrated or transiently expressed luciferase reporters repressed by endogenous miR-30 and let-7 miRNAs and identified 163 putative miRNA inhibitors. We report that compounds relieving miRNA-mediated repression via stress induction are infrequent; we have found only two compounds that reproducibly induced stress granules and relieved miRNA-targeted reporter repression. However, we have found that this assay type readily yields non-specific (miRNA-independent) stimulators of luciferase reporter activity. Furthermore, our data provide partial support for previously published miRNA pathway modulators; the most notable intersections were found among anthracyclines, dopamine derivatives, flavones, and stilbenes. Altogether, our results underscore the importance of appropriate negative controls in development of small compound inhibitors of the miRNA pathway. This particularly concerns validation strategies, which would greatly profit from assays that fundamentally differ from the routinely employed miRNA-targeted reporter assays.
journal_name
Front Genetjournal_title
Frontiers in geneticsauthors
Brustikova K,Sedlak D,Kubikova J,Skuta C,Solcova K,Malik R,Bartunek P,Svoboda Pdoi
10.3389/fgene.2018.00045subject
Has Abstractpub_date
2018-02-27 00:00:00pages
45issn
1664-8021journal_volume
9pub_type
杂志文章abstract::The genetic predisposition to chronic kidney disease (CKD) has been widely evaluated especially using the genome-wide association studies, which highlighted some novel genetic susceptibility variants in many genes, and estimated glomerular filtration rate to diagnose and stage CKD. Of these variants, rs7805747 in PRKA...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00573
更新日期:2018-12-03 00:00:00
abstract::Known as the "fifth RNA nucleotide", pseudouridine (Ψ or psi) is the first-discovered and most abundant RNA modification occurring at the Uridine site, and it plays a prominent role in a number of biological processes. Thousands of Ψ sites have been identified within different biological contexts thanks to the advance...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00088
更新日期:2020-03-12 00:00:00
abstract::Background:NKX2-1 related disorders (also known as brain-lung-thyroid syndrome or benign hereditary chorea 1) are associated with a wide spectrum of symptoms. The core features are various movement disorders, characteristically chorea, less frequently myoclonus, dystonia, ataxia; thyroid disease; and lung involvement....
journal_title:Frontiers in genetics
pub_type:
doi:10.3389/fgene.2018.00335
更新日期:2018-08-22 00:00:00
abstract::Fragile-X syndrome is one of the most common forms of inherited mental retardation and autistic behaviors. The reduction/absence of the functional FMRP protein, coded by the X-linked Fmr1 gene in humans, is responsible for the syndrome. Patients exhibit a variety of symptoms predominantly linked to the function of FMR...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2019.00010
更新日期:2019-02-13 00:00:00
abstract::A rapidly increasing number of reports on dysregulated long intergenic non-coding RNA (lincRNA) expression across numerous types of cancers indicates that aberrant lincRNA expression may be a major contributor to tumorigenesis. Marek's disease (MD) is a T cell lymphoma of chickens induced by Marek's disease virus (MDV...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.01122
更新日期:2019-11-14 00:00:00
abstract::Malaria remains a major healthcare risk to growing economies like India, and a chromosome-level reference genome of Anopheles stephensi is critical for successful vector management and understanding of vector evolution using comparative genomics. We report chromosome-level assemblies of an Indian strain, STE2, and a P...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.565626
更新日期:2020-11-16 00:00:00
abstract::Reliable phenotypes are paramount for meaningful quantification of genetic variation and for estimating individual breeding values on which genetic selection is based. In this paper, we assert that genetic improvement of host tolerance to disease, although desirable, may be first of all handicapped by the ability to o...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2012.00265
更新日期:2012-12-14 00:00:00
abstract::The timing of the transition to flowering is carefully controlled by plants in order to optimize sexual reproduction and the ensuing production of seeds, grains, and fruits. The genetic networks that regulate floral induction are best characterized in the temperate eudicot Arabidopsis in which the florigen gene FT pla...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2015.00050
更新日期:2015-02-19 00:00:00
abstract::Cellular commitment and differentiation involve highly coordinated mechanisms by which tissue-specific genes are activated while others are repressed. These mechanisms rely on the activity of specific transcription factors, chromatin remodeling enzymes, and higher-order chromatin organization in order to modulate tran...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2020.578712
更新日期:2020-09-18 00:00:00
abstract::During plant-pathogen interactions, pathogens secrete many rapidly evolving, small secreted proteins (SSPs) that can modify plant defense and permit pathogens to colonize plant tissue. The fungal pathogen Zymoseptoria tritici is the causal agent of Septoria tritici blotch (STB), one of the most important foliar diseas...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00469
更新日期:2020-05-12 00:00:00
abstract::Aberrant, misfolded, and mislocalized proteins are often toxic to cells and result in many human diseases. All proteins and their mRNA templates are subject to quality control. There are several distinct mechanisms that control the quality of mRNAs and proteins during translation at the ribosome. mRNA quality control ...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2018.00431
更新日期:2018-10-04 00:00:00
abstract::People want to live long, healthy lives. Previous surveys suggest very limited interest in much longer lifespans, but we show that stipulating good health changes responses to favor longer lives by an order of magnitude. Advances in aging research hold out hope for greatly slowed aging with associated good health. Und...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2015.00353
更新日期:2016-01-20 00:00:00
abstract::The New England Centenarian Study (NECS) was founded in 1994 as a longitudinal study of centenarians to determine if centenarians could be a model of healthy human aging. Over time, the NECS along with other centenarian studies have demonstrated that the majority of centenarians markedly delay high mortality risk-asso...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2012.00277
更新日期:2012-11-30 00:00:00
abstract::Recent work shows strong evidence of ancestry-based assortative mating in spouse pairs of the older generation of the Framingham Heart Study. Here, we extend this analysis to two studies of human longevity: the Long Life Family Study (LLFS), and the New England Centenarian Study (NECS). In the LLFS, we identified 890 ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2017.00186
更新日期:2017-11-21 00:00:00
abstract::Pathogenic microorganism analysis based on next-generation sequencing technology is an important tool for clinical diagnosis, public health surveillance, and outbreak investigation. However, scientific researchers without the relevant background lack the time, training, or infrastructure to use large data sets or inst...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.01007
更新日期:2020-08-31 00:00:00
abstract::Genotype imputation is a powerful tool for increasing statistical power in an association analysis. Meta-analysis of multiple study datasets also requires a substantial overlap of SNPs for a successful association analysis, which can be achieved by imputation. Quality of imputed datasets is largely dependent on the so...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00034
更新日期:2019-02-05 00:00:00
abstract:Background:Cystinuria is a rare genetic disorder characterized by defective renal reabsorption of cystine, ornithine, arginine, and lysine. The increased urinary excretion of cystine results in the development of cystine urolithiasis (CU). The mutated SLC3A1 and SLC7A9 genes are the cause of CU, a global disorder. Its ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00074
更新日期:2020-02-18 00:00:00
abstract::Nile tilapia (Oreochromis niloticus) is among the most important finfish in aquaculture, particularly in Asia. Numerous genetically improved strains of Nile tilapia have been developed and disseminated through formal and informal channels to hatcheries, many of which operate at a relatively small scale in developing c...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.594722
更新日期:2020-12-01 00:00:00
abstract::Ethylmalonic encephalopathy (EE) is a very rare autosomal recessive metabolic disorder that primarily affects children. Less than one hundred EE patients have been diagnosed worldwide. The clinical manifestations include chronic diarrhea, petechiae, orthostatic acrocyanosis, psychomotor delay and regression, seizures,...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00341
更新日期:2020-04-17 00:00:00
abstract::Selection for improved host response to infectious disease offers a desirable alternative to chemical treatment but has proven difficult in practice, due to low heritability estimates of disease traits. Disease data from field studies is often binary, indicating whether an individual has become infected or not followi...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2012.00215
更新日期:2012-10-22 00:00:00
abstract:Background:This study searched for immune-related long noncoding RNAs (lncRNAs) to predict the prognosis of patients with cervical cancer. Method:We obtained immunologically relevant lncRNA expression profiles and clinical follow-up data from cervical cancer patients from The Cancer Genome Atlas database and the Molec...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.533628
更新日期:2020-10-14 00:00:00
abstract::Oxidative stress is one of the crucial mediators of varicocele-related male infertility. Recently, roles of long noncoding RNAs (lncRNAs) in oxidative stress have begun to emerge, however, little is known about their role in male infertility. The aim of this study was to determine the role of lncRNA SLC7A11-AS1 in var...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.01015
更新日期:2020-09-11 00:00:00
abstract::Diabetes mellitus represents a group of complex metabolic diseases that result in impaired glucose homeostasis, which includes destruction of β-cells or the failure of these insulin-secreting cells to compensate for increased metabolic demand. Despite a strong interest in characterizing the transcriptome of the differ...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2014.00200
更新日期:2014-07-01 00:00:00
abstract::Liver fibrosis resulting from chronic liver damage constitutes a major health care burden worldwide; however, no antifibrogenic agents are currently available. Our previous study reported that the small molecule NPLC0393 extracted from the herb Gynostemma pentaphyllum exerts efficient antifibrotic effects both in vivo...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.594824
更新日期:2020-11-04 00:00:00
abstract::Pacu (Piaractus mesopotamicus) is a Neotropical fish of major importance for South American aquaculture. Septicemia caused by Aeromonas hydrophila bacteria is currently considered a substantial threat for pacu aquaculture that have provoked infectious disease outbreaks with high economic losses. The understanding of m...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00604
更新日期:2020-06-09 00:00:00
abstract::Some candidate genes have been robustly reported to be associated with complex traits, such as the fat mass and obesity-associated (FTO) gene on body mass index (BMI), and the fibroblast growth factor 5 (FGF5) gene on blood pressure levels. It is of interest to know whether an environmental factor (E) can attenuate or...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00331
更新日期:2020-05-08 00:00:00
abstract::Ionizing radiation (IR) is a high-energy radiation whose biological effects depend on the irradiation doses. Low-dose radiation (LDR) is delivered during medical diagnoses or by an exposure to radioactive elements and has been linked to the occurrence of chronic diseases, such as leukemia and cardiovascular diseases. ...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2020.566244
更新日期:2020-10-02 00:00:00
abstract::As a conserved protein family, WRKY has been shown to be involved in multiple biological processes in plants. However, the mechanism of functional diversity for WRKYs in pepper has not been well elucidated. Here, a total of 223 WRKY members from solanaceae crops including pepper, tomato and potato, were analyzed using...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00492
更新日期:2019-05-28 00:00:00
abstract::Genome-wide Association Studies (GWAS) result in millions of summary statistics ("z-scores") for single nucleotide polymorphism (SNP) associations with phenotypes. These rich datasets afford deep insights into the nature and extent of genetic contributions to complex phenotypes such as psychiatric disorders, which are...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2016.00015
更新日期:2016-02-16 00:00:00
abstract::The carbon catabolite repression 4 (CCR4)-negative on TATA-less (NOT) complex serves as one of the major deadenylases of eukaryotes. Although it was originally identified and characterized in yeast, recent studies have revealed that the CCR4-NOT complex also exerts important functions in mammals, -including humans. Ho...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2014.00286
更新日期:2014-08-21 00:00:00