Cell-Based Reporter System for High-Throughput Screening of MicroRNA Pathway Inhibitors and Its Limitations.

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 Genet

journal_title

Frontiers in genetics

authors

Brustikova K,Sedlak D,Kubikova J,Skuta C,Solcova K,Malik R,Bartunek P,Svoboda P

doi

10.3389/fgene.2018.00045

subject

Has Abstract

pub_date

2018-02-27 00:00:00

pages

45

issn

1664-8021

journal_volume

9

pub_type

杂志文章
  • Functional Prediction of Chronic Kidney Disease Susceptibility Gene PRKAG2 by Comprehensively Bioinformatics Analysis.

    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

    authors: Wang E,Zhao H,Zhao D,Li L,Du L

    更新日期:2018-12-03 00:00:00

  • PIANO: A Web Server for Pseudouridine-Site (Ψ) Identification and Functional Annotation.

    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

    authors: Song B,Tang Y,Wei Z,Liu G,Su J,Meng J,Chen K

    更新日期:2020-03-12 00:00:00

  • NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement.

    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

    authors: Balicza P,Grosz Z,Molnár V,Illés A,Csabán D,Gézsi A,Dézsi L,Zádori D,Vécsei L,Molnár MJ

    更新日期:2018-08-22 00:00:00

  • Drosophila melanogaster as a Model to Study the Multiple Phenotypes, Related to Genome Stability of the Fragile-X Syndrome.

    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

    authors: Specchia V,Puricella A,D'Attis S,Massari S,Giangrande A,Bozzetti MP

    更新日期:2019-02-13 00:00:00

  • Linc-GALMD1 Regulates Viral Gene Expression in the Chicken.

    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

    authors: He Y,Han B,Ding Y,Zhang H,Chang S,Zhang L,Zhao C,Yang N,Song J

    更新日期:2019-11-14 00:00:00

  • A Near-Chromosome Level Genome Assembly of Anopheles stephensi.

    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

    authors: Chida AR,Ravi S,Jayaprasad S,Paul K,Saha J,Suresh C,Whadgar S,Kumar N,Rao K R,Ghosh C,Choudhary B,Subramani S,Srinivasan S

    更新日期:2020-11-16 00:00:00

  • The first step toward genetic selection for host tolerance to infectious pathogens: obtaining the tolerance phenotype through group estimates.

    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

    authors: Doeschl-Wilson AB,Villanueva B,Kyriazakis I

    更新日期:2012-12-14 00:00:00

  • Three Medicago MtFUL genes have distinct and overlapping expression patterns during vegetative and reproductive development and 35S:MtFULb accelerates flowering and causes a terminal flower phenotype in Arabidopsis.

    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

    authors: Jaudal M,Zhang L,Che C,Putterill J

    更新日期:2015-02-19 00:00:00

  • Chromatin Landscape During Skeletal Muscle Differentiation.

    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

    authors: Hernández-Hernández O,Ávila-Avilés RD,Hernández-Hernández JM

    更新日期:2020-09-18 00:00:00

  • Wheat Encodes Small, Secreted Proteins That Contribute to Resistance to Septoria Tritici Blotch.

    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

    authors: Zhou B,Benbow HR,Brennan CJ,Arunachalam C,Karki SJ,Mullins E,Feechan A,Burke JI,Doohan FM

    更新日期:2020-05-12 00:00:00

  • Lost in Translation: Ribosome-Associated mRNA and Protein Quality Controls.

    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

    authors: Karamyshev AL,Karamysheva ZN

    更新日期:2018-10-04 00:00:00

  • Great Desire for Extended Life and Health amongst the American Public.

    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

    authors: Donner Y,Fortney K,Calimport SR,Pfleger K,Shah M,Betts-LaCroix J

    更新日期:2016-01-20 00:00:00

  • The genetics of extreme longevity: lessons from the new England centenarian study.

    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

    authors: Sebastiani P,Perls TT

    更新日期:2012-11-30 00:00:00

  • Assortative Mating by Ethnicity in Longevous Families.

    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

    authors: Sebastiani P,Gurinovich A,Bae H,Andersen SL,Perls TT

    更新日期:2017-11-21 00:00:00

  • MDACP: A Pathogen Genome and Metagenome Analysis Cloud Platform.

    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

    authors: Han N,Miao J,Zhang T,Qiang Y,Peng X,Li X,Zhang W

    更新日期:2020-08-31 00:00:00

  • Evaluating the Accuracy of Imputation Methods in a Five-Way Admixed Population.

    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

    authors: Schurz H,Müller SJ,van Helden PD,Tromp G,Hoal EG,Kinnear CJ,Möller M

    更新日期:2019-02-05 00:00:00

  • Genetic and Clinical Analyses of 13 Chinese Families With Cystine Urolithiasis and Identification of 15 Novel Pathogenic Variants in SLC3A1 and SLC7A9.

    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

    authors: Li C,Yang Y,Zheng Y,Shen F,Liu L,Li Y,Li L,Zhao Y

    更新日期:2020-02-18 00:00:00

  • Distinguishing Between Nile Tilapia Strains Using a Low-Density Single-Nucleotide Polymorphism Panel.

    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

    authors: Hamilton MG,Lind CE,Barman BK,Velasco RR,Danting MJC,Benzie JAH

    更新日期:2020-12-01 00:00:00

  • Novel Compound Heterozygous Variants of ETHE1 Causing Ethylmalonic Encephalopathy in a Chinese Patient: A Case Report.

    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

    authors: Chen X,Han L,Yao H

    更新日期:2020-04-17 00:00:00

  • Bias, accuracy, and impact of indirect genetic effects in infectious diseases.

    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

    authors: Lipschutz-Powell D,Woolliams JA,Bijma P,Pong-Wong R,Bermingham ML,Doeschl-Wilson AB

    更新日期:2012-10-22 00:00:00

  • Six-lncRNA Immune Prognostic Signature for Cervical Cancer.

    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

    authors: Chen Q,Hu L,Huang D,Chen K,Qiu X,Qiu B

    更新日期:2020-10-14 00:00:00

  • Transcript Isoforms of SLC7A11-AS1 Are Associated With Varicocele-Related Male Infertility.

    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

    authors: Sanei-Ataabadi N,Mowla SJ,Nasr-Esfahani MH

    更新日期:2020-09-11 00:00:00

  • The Missing lnc(RNA) between the pancreatic β-cell and diabetes.

    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

    authors: Kameswaran V,Kaestner KH

    更新日期:2014-07-01 00:00:00

  • The Active Constituent From Gynostemma Pentaphyllum Prevents Liver Fibrosis Through Regulation of the TGF-β1/NDRG2/MAPK Axis.

    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

    authors: Huang H,Wang K,Liu Q,Ji F,Zhou H,Fang S,Zhu J

    更新日期:2020-11-04 00:00:00

  • Transcriptome Profiling of Pacu (Piaractus mesopotamicus) Challenged With Pathogenic Aeromonas hydrophila: Inference on Immune Gene Response.

    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

    authors: Mastrochirico-Filho VA,Hata ME,Kuradomi RY,de Freitas MV,Ariede RB,Pinheiro DG,Robledo D,Houston R,Hashimoto DT

    更新日期:2020-06-09 00:00:00

  • Using Genetic Risk Score Approaches to Infer Whether an Environmental Factor Attenuates or Exacerbates the Adverse Influence of a Candidate Gene.

    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

    authors: Lin WY,Lin YS,Chan CC,Liu YL,Tsai SJ,Kuo PH

    更新日期:2020-05-08 00:00:00

  • Organ-Specific Effects of Low Dose Radiation Exposure: A Comprehensive Review.

    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

    authors: Shin E,Lee S,Kang H,Kim J,Kim K,Youn H,Jin YW,Seo S,Youn B

    更新日期:2020-10-02 00:00:00

  • Comparative Genomic Analysis Reveals Extensive Genetic Variations of WRKYs in Solanaceae and Functional Variations of CaWRKYs in Pepper.

    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

    authors: Cheng Y,Ahammed GJ,Yao Z,Ye Q,Ruan M,Wang R,Li Z,Zhou G,Wan H

    更新日期:2019-05-28 00:00:00

  • Estimating Effect Sizes and Expected Replication Probabilities from GWAS Summary Statistics.

    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

    authors: Holland D,Wang Y,Thompson WK,Schork A,Chen CH,Lo MT,Witoelar A,Schizophrenia Working Group of the Psychiatric Genomics Consortium.,Enhancing Neuro Imaging Genetics through Meta Analysis Consortium.,Werge T,O'Donovan M,Andreassen OA

    更新日期:2016-02-16 00:00:00

  • Multifunctional roles of the mammalian CCR4-NOT complex in physiological phenomena.

    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

    authors: Shirai YT,Suzuki T,Morita M,Takahashi A,Yamamoto T

    更新日期:2014-08-21 00:00:00