Article
|
Open Access
Featured
-
-
Article
| Open AccessLight-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice
Inhibition of microRNAs using antimiRs is a potential therapeutic option for a number of diseases, but systemic inhibition may cause adverse effects. Here the authors develop light-activated antimiRs directed against miR-92a, and show localized inhibition in the skin and improved wound healing in diabetic mice.
- Tina Lucas
- , Florian Schäfer
- & Stefanie Dimmeler
-
Article
| Open AccessComputational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer
Dysregulation of microRNAs is thought to be important for metastasis in castration-resistant prostate cancer (CRPC), but its drivers are unknown. Here, the authors use computational analysis to identify HOXC6 and NKX2-2 in addition to AR as alternative drivers of dysregulated miRNA expression in CRPC.
- Mengzhu Xue
- , Haiyue Liu
- & Peng Wang
-
Article
| Open AccessMicroRNA miR-23a cluster promotes osteocyte differentiation by regulating TGF-β signalling in osteoblasts
Control of osteocyte differentiation is not well understood. Here the authors show that the miR-23 cluster represses the TGF-β signalling repressor Prdm16 in osteoblasts, thus enhancing osteocyte differentiation and a low bone mass phenotype.
- Huan-Chang Zeng
- , Yangjin Bae
- & Brendan H. Lee
-
Article
| Open AccessMicroRNA-92a is a circadian modulator of neuronal excitability in Drosophila
Accumulating evidence suggests that microRNAs play a role in circadian regulation. Here the authors show that in theDrosophila brain, mir-92a suppresses the excitability of PDF neurons—key circadian pacemaker cells in Drosophila—via inhibiting the translation of its target sirt2.
- Xiao Chen
- & Michael Rosbash
-
Article
| Open AccessA microRNA-initiated DNAzyme motor operating in living cells
Synthetic DNA nanomachines have been designed to perform a variety of tasksin vitro. Here, the authors build a nanomotor system that integrates a DNAzyme and DNA track on a gold nanoparticle, to facilitate cellular uptake, and apply it as a real-time miRNA imaging tool in living cells.
- Hanyong Peng
- , Xing-Fang Li
- & X. Chris Le
-
Article
| Open AccessmicroRNA-17 family promotes polycystic kidney disease progression through modulation of mitochondrial metabolism
Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening genetic disease that leads to renal failure. Here Hajarniset al. show that miR-17 modulates cyst progression in ADPKD through metabolic reprogramming of mitochondria and its inhibition slows cyst development and improves renal functions.
- Sachin Hajarnis
- , Ronak Lakhia
- & Vishal Patel
-
Article
| Open AccessThe impact of microRNAs on transcriptional heterogeneity and gene co-expression across single embryonic stem cells
MicroRNAs can posttranscriptionally repress multiple targets in a cell population. Here the authors use single-cell sequencing to investigate the effects of an individual miRNA on transcriptional heterogeneity and gene co-expression
- Gennaro Gambardella
- , Annamaria Carissimo
- & Robert Blelloch
-
Article
| Open AccessInfected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria
Inflammatory response to malaria pathogen Plasmodium falciparumcan be triggered by infected red blood cell-derived extracellular vesicles (EVs). This study shows these EVs contain functional microRNA-Argonaute 2 complex that modulates gene expression and alter vascular barrier properties.
- Pierre-Yves Mantel
- , Daisy Hjelmqvist
- & Matthias Marti
-
Article
| Open AccessA regulatory circuit of miR-125b/miR-20b and Wnt signalling controls glioblastoma phenotypes through FZD6-modulated pathways
Glioblastoma (GBM) is classified as proneural (PN), neural, mesenchymal (MES) and classical GBM. Here the authors show that Wnt signalling, miR-125b and miR-20b establish a regulatory circuitry including FZD6 which distinguishes PN from the MES subtype.
- Tianzhi Huang
- , Angel A. Alvarez
- & Shi-Yuan Cheng
-
Article
| Open AccessThe microRNA cluster miR-183/96/182 contributes to long-term memory in a protein phosphatase 1-dependent manner
Protein phosphatase1 (PP1), a signalling and transcriptional regulator, and epigenetic modulator is known to be a memory suppressor. Here the authors show that memory control by PP1 involves the microRNA cluster miR-183/96/182, and that this cluster is selectively regulated during memory formation in mice.
- Bisrat T. Woldemichael
- , Ali Jawaid
- & Isabelle M. Mansuy
-
Article
| Open AccessTarget-dependent biogenesis of cognate microRNAs in human cells
MicroRNAs are a widespread regulatory mechanism and are themselves extensively regulated. Here the authors show regulated miRNA biogenesis by the target mRNA, a layer of regulation that modulates miRNA levels dependent on target availability.
- Mainak Bose
- & Suvendra N. Bhattacharyya
-
Article
| Open AccessmiR-93 regulates Msk2-mediated chromatin remodelling in diabetic nephropathy
Podocyte injury is central to kidney dysfunction in diabetic nephropathy. Here the authors show that Msk2 is a target of miR-93 and this interaction mediates pathogenic chromatin remodelling in diabetic nephropathy.
- Shawn S. Badal
- , Yin Wang
- & Farhad R. Danesh
-
Article
| Open AccessMicroRNA-125b-5p mimic inhibits acute liver failure
miR125b-5p has been associated with acute liver failure. Here the authors show that this miRNA targets Keap1 and activates Nrf2 to inhibit liver cell death after APAP or FAS toxicity, plus they show that a miR125b-5p mimic can inhibit ALF in mice.
- Dakai Yang
- , Qinggong Yuan
- & Amar Deep Sharma
-
Article
| Open AccessTumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression
miRNAs can function either as proto-oncogenes or tumour suppressors in several cancers; however their function in tumour initiating cells is unclear. Here, Zhang et al. show that tumour initiating cell-specific miR-1246 and miR-1290 promote lung cancer initiation and metastasis and could serve as prognostic markers.
- Wen Cai Zhang
- , Tan Min Chin
- & Bing Lim
-
Article
| Open AccessFasting induces a subcutaneous-to-visceral fat switch mediated by microRNA-149-3p and suppression of PRDM16
Visceral adiposity is associated with metabolic diseases, whereas subcutaneous adiposity is comparatively benign. Here, the authors report that subcutaneous adipose tissue adopts visceral-like characteristics in response to prolonged fasting, and show this is mediated by miR-149-3p and its target, PRDM16.
- Hanying Ding
- , Shasha Zheng
- & Xiaohong Jiang
-
Article
| Open AccessArgonaute-associated short introns are a novel class of gene regulators
MicroRNAs are important small regulatory RNAs produced by sequential Drosha and Dicer cleavage. Here the authors describe 'agotrons', a subclass of small RNAs that bypass the canonical biogenesis machinery.
- Thomas B. Hansen
- , Morten T. Venø
- & Jørgen Kjems
-
Article
| Open AccessmiR-216b regulation of c-Jun mediates GADD153/CHOP-dependent apoptosis
The transcription factor CHOP/GADD153 regulates apoptosis in response to the unfolded protein response. Here the authors show that CHOP/GADD153 regulates the expression of miR-216b, which targets c-Jun and sensitizes cells to ER stress-dependent apoptosis.
- Zhenhua Xu
- , Yiwen Bu
- & J. Alan Diehl
-
Article
| Open AccessExosomal microRNA miR-92a concentration in serum reflects human brown fat activity
Exosomes are RNA-containing lipid vesicles with roles in inter-tissue crosstalk. Here the authors show that exosome release from brown adipocytes is increased upon thermogenic activation, both in vitro and in vivo, and demonstrate that serum levels of exosomal miR-92 reflect brown fat activity in humans.
- Yong Chen
- , Joschka J. Buyel
- & Alexander Pfeifer
-
Article
| Open AccessmiR-22 has a potent anti-tumour role with therapeutic potential in acute myeloid leukaemia
Mir-22 has been shown to be an oncogenic microRNA in breast cancer and myelodysplastic syndrome. Here, the authors show that mir-22 functions as a tumour suppressor in de novoacute myeloid leukaemia by inhibiting the expression of several oncogenes and that restoring mir-22 expression suppresses AML progression.
- Xi Jiang
- , Chao Hu
- & Jianjun Chen
-
Article
| Open AccessmiRNA863-3p sequentially targets negative immune regulator ARLPKs and positive regulator SERRATE upon bacterial infection
Small RNA plays an important role in regulating the plant defence against bacterial pathogens. Here the authors propose that miR863-3p acts to fine-tune the timing of defence responses by sequentially silencing negative and positive regulators of the plant immune response.
- Dongdong Niu
- , Yifan E. Lii
- & Hailing Jin
-
Article
| Open AccessHost gene constraints and genomic context impact the expression and evolution of human microRNAs
Recent miRNAs tend to emerge within coding genes. Here, by analysing miRNA expression data from six species and comparing genomes from 13 species, the authors report that host genes may provide stronger expression constraints to intragenic miRNAs in the long run.
- Gustavo S. França
- , Maria D. Vibranovski
- & Pedro A. F. Galante
-
Article
| Open AccessDysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer
The orphan nuclear receptor COUP-TFII is highly expressed in metastatic prostate cancers and its overexpression accelerates prostate tumour progression in mouse models. Here, the author show that that loss of miR-101 and miR-27a in prostate cancer cells can lead to COUP-TFII expression which in turn directly regulates FOXM1 and CENPFfavouring prostate cancer metastasis.
- Shih-Chieh Lin
- , Chung-Yang Kao
- & Ming-Jer Tsai
-
Article
| Open AccessmiR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR–p-PI3K/AKT-c-JUN
Although miR-related mechanisms have been implicated in nasopharyngeal carcinoma (NPC), a precise role for miR-3188 has not been reported in this context. Here, Zhao et al. show that FOXO1-induced miR-3188 acts as a tumour suppressor in NPC by regulating the axis mTOR/PI3K/Akt/c-Jun.
- Mengyang Zhao
- , Rongcheng Luo
- & Weiyi Fang
-
Article
| Open AccessMicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation
G protein-coupled receptors APLNR and CXCR4 are crucial for vascular development. Here, the authors show that these two signaling pathways communicate and that in response to blood flow APLNR signaling induces a decrease in CXCR4 expression via miR-139-5p, thereby restricting CXCR4 expression to the non-flow exposed tip cells in the retinal vasculature.
- Irinna Papangeli
- , Jongmin Kim
- & Hyung J. Chun
-
Article
| Open AccessCircular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs
Circular RNAs are formed from exon back-splicing, the significance of these endogenous RNAs is beginning to be unraveled. Here, the authors identify thousands of circular RNAs differentially expressed between normal and cancer tissues and show that an abundant circular RNA generated from HIPK3regulates cell growth.
- Qiupeng Zheng
- , Chunyang Bao
- & Shenglin Huang
-
Article
| Open AccessA miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer
The formation of blood vessels in tumours, angiogenesis, is a promising target for therapy. Here, the authors show that microRNA192 has anti-angiogenic functions and negatively regulates EGR1 and HOXB9, and that delivery of this microRNA to tumours in vivocan reduce angiogenesis and tumour growth.
- Sherry Y. Wu
- , Rajesha Rupaimoole
- & Anil K. Sood
-
Article
| Open AccessA Molecular Chipper technology for CRISPR sgRNA library generation and functional mapping of noncoding regions
The interrogation of noncoding regions of the genome with CRISPR strategies requires dense and, ideally, inexpensive libraries to ensure coverage and customisation. Here the authors present 'Molecular Chipper' that uses fragmentation to generate guide RNAs from input DNA.
- Jijun Cheng
- , Christine A. Roden
- & Jun Lu
-
Article
| Open AccessExosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1
The tumor microenviroment can influence cancer progression and response to therapy. In this study, the authors show that miR21 is transferred through exosomes from cancer-associated fibroblasts and adipocytes to ovarian cancer cells where it modulates drug resistance by its direct target APAF1.
- Chi Lam Au Yeung
- , Ngai-Na Co
- & Samuel C. Mok
-
Article
| Open AccessMicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression
Liver fibrosis is a pathogenic driver of many liver diseases, so understanding its regulation might open the door to new therapies. Here the authors perform a screen for miRNA candidates and identify that miR-378 inhibits liver fibrosis in mice by interfering with Hedgehog signalling in hepatic stellate cells.
- Jeongeun Hyun
- , Sihyung Wang
- & Youngmi Jung
-
Article
| Open AccessmiR-34 activity is modulated through 5′-end phosphorylation in response to DNA damage
MiR-34 is a tumour suppressor microRNA known to be upregulated by p53 after DNA damage and plays a critical role in cell cycle arrest and apoptosis. Here the authors show the cell maintains an inactive pool of miR-34 which is rapidly activated after damage via ATM-dependent phosphorylation.
- David W. Salzman
- , Kotoka Nakamura
- & Joanne B. Weidhaas
-
Article
| Open AccessDifferential TGFβ pathway targeting by miR-122 in humans and mice affects liver cancer metastasis
MiR-122 levels correlate with metastasis in human liver cancer but not in mouse models. Here the authors show that miR-122 targets TGFßR1 in mice but TGFß1 in humans, that swapping this specificity affects metastasis, and that many other receptor-ligand pairs are differentially targeted by miRNAs across species.
- Shenyi Yin
- , Yu Fan
- & Jianzhong Jeff Xi
-
Article
| Open AccessThe TLX-miR-219 cascade regulates neural stem cell proliferation in neurodevelopment and schizophrenia iPSC model
Dysregulation of microRNAs has been implicated in neurodevelopmental disorders, including schizophrenia. Here the authors show that the TLX-miR-219 cascade regulates the proliferation of neural stem cells during normal development, and this pathway is dysregulated in a schizophrenia iPSC model.
- Kiyohito Murai
- , Guoqiang Sun
- & Yanhong Shi
-
Article
| Open AccessOsteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation
In previous studies the authors discovered that miR-214 inhibits osteoblastic bone formation. Here they extend on these findings, using ovariectomized mice and samples from patients with bone fractures, to show that miR-214 is a mediator of osteoclast-osteoblast crosstalk.
- Defang Li
- , Jin Liu
- & Ge Zhang
-
Article
| Open AccessCell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects
A challenge in regenerative medicine is the development of cell-free, non-immunogenic miRNA-delivering scaffolds. Here the authors design a cell-free scaffold capable of efficient and prolonged delivery of miRNA-26a to endogenous cells and show that it can regenerate a full-thickness calvarial bone defect in mice.
- Xiaojin Zhang
- , Yan Li
- & Peter X. Ma
-
Article
| Open AccessRegulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through
The miR-141/200 familly of micro RNAs control oxidative stress and impact on ovarian tumorigenesis. Here the authors show that the transcription of miR-200c/141 is regulated through transcriptional read-through of the upstream gene PTPN6, and DNA looping linking the PTPN6 and miR-200c/141 promoters.
- Luciana Batista
- , Brigitte Bourachot
- & Fatima Mechta-Grigoriou
-
Article
| Open AccessThe Six1 oncoprotein downregulates p53 via concomitant regulation of RPL26 and microRNA-27a-3p
p53 is a tumour suppressor that is mutated in a large number of cancers and its expression is controlled largely by the ubiquitin ligase MDM2. Here, the authors show that the homeoprotein, Six1, can regulate p53 in an MDM2- independent manner via regulation of miR-27a and the RNA binding protein, RPL26.
- Christina G. Towers
- , Anna L. Guarnieri
- & Heide L. Ford
-
Article
| Open AccessMicroRNA miR124 is required for the expression of homeostatic synaptic plasticity
GluA2-lacking AMPA receptors are known to play a role in homeostatic plasticity. Here, the authors show that spiking activity blockade disinhibits mir124 transcription, which in turn suppresses GluA2 mRNA translation, thereby contributing to synaptic upscaling in hippocampal cells.
- Qingming Hou
- , Hongyu Ruan
- & Heng-Ye Man
-
Article
| Open AccessmiRNA–target chimeras reveal miRNA 3′-end pairing as a major determinant of Argonaute target specificity
microRNAs (miRNAs) act as sequence-specific guides for Argonaute (AGO) proteins. By using a modified AGO HITS-CLIP strategy that enriches miRNAs ligated to their endogenous mRNA targets, here the authors show that miRNA 3' end pairing is a general determinant of AGO binding specificity.
- Michael J. Moore
- , Troels K. H. Scheel
- & Robert B. Darnell
-
Article
| Open AccessSTAT5-regulated microRNA-193b controls haematopoietic stem and progenitor cell expansion by modulating cytokine receptor signalling
MicroRNAs regulate haematopoietic stem cell (HSC) development to ensure the correct generation of blood cells. Haetscher et al. show in mice that miR-193b controls the life-long self-renewal ability of HSCs via AKT and STAT5 pathways, with loss of miR-193b accelerating HSC expansion and reducing differentiation.
- Nadine Haetscher
- , Yonatan Feuermann
- & Michael A. Rieger
-
Article
| Open AccessMicroRNA–mRNA interactions underlying colorectal cancer molecular subtypes
Colorectal cancer subtypes can be distinguished by their different biological and molecular properties. Here the authors present microRNA Master Regulator Analysis, a tool to identify microRNAs driving subtype-specific gene expression and cancer variation.
- Laura Cantini
- , Claudio Isella
- & Enzo Medico
-
Article
| Open AccessmiR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth
The synergism between c-MYC and miR-17-19b plays an important role in lymphoma initiation. In this study, the authors identify a panel of targets co-regulated by miR-17-19b and in MYC-driven lymphoma and unravel the molecular mechanism through which miR-17-19b inhibits MYCtranslation.
- Marija Mihailovich
- , Michael Bremang
- & Tiziana Bonaldi
-
Article
| Open AccessAberrantly expressed miR-582-3p maintains lung cancer stem cell-like traits by activating Wnt/β-catenin signalling
Despite the absence of frequent mutations of key components of Wnt/β-catenin signalling, this pathway is often constitutively activated in non-small cell lung carcinoma. In this study, the authors demonstrate the inhibitory effect of miR-582-3p on negative regulators of the Wnt/β-catenin pathway which is consequently triggered to sustain lung tumour growth.
- Lishan Fang
- , Junchao Cai
- & Mengfeng Li
-
Article
| Open AccessmiR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program
Fibroblast activity is regulated by tissue macrophages. Here the authors show that two miRNAs regulated by IL-4 and IL-13 in macrophages target SOCS1 and PPARγ and modulate profibrogenic macrophage program in vitro and in vivo, and that alterations of these miRNAs are found in fibrosis.
- Shicheng Su
- , Qiyi Zhao
- & Erwei Song
-
Article |
PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells
α2δ1 is a marker of liver tumour-initiating cells. Here the authors show that PBX3 is necessary and sufficient for tumour initiation by α2δ1+ cells by regulating transcription of stemness genes, and that PBX3 is targeted by four miRNAs downregulated in α2δ1+ cells.
- Haibo Han
- , Yantao Du
- & Zhiqian Zhang
-
Article
| Open AccessmiR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways
MicroRNAs of the miR-34/449 family initiate formation of multiciliated cells through the suppression of cell cycle genes and Notch. Here the authors show that miR-34/449 also regulate the assembly of an apical actin network necessary for basal body anchoring by regulating the expression of R-Ras.
- Benoît Chevalier
- , Anna Adamiok
- & Brice Marcet
-
Article
| Open AccessPostnatal β-cell maturation is associated with islet-specific microRNA changes induced by nutrient shifts at weaning
Pancreatic β-cells are less responsive to changes in glucose concentration in newborn than in adult rats. Here, the authors show that functional β-cell maturation is associated with changes in miRNA expression induced by nutritional shifts at the suckling-to-weaning transition.
- Cécile Jacovetti
- , Scot J. Matkovich
- & Romano Regazzi
-
Article
| Open Accessp75NTR-dependent activation of NF-κB regulates microRNA-503 transcription and pericyte–endothelial crosstalk in diabetes after limb ischaemia
Vascular function and repair is impaired in patients with diabetes. Here, Caporali et al.report that activation of the neurotrophin receptor in vascular endothelial cells induces the antiangiogenic miR-503, which impairs the function of neighbouring pericytes upon microparticle-mediated transfer.
- Andrea Caporali
- , Marco Meloni
- & Costanza Emanueli
-
Article |
miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3
microRNAs have emerged as important components of numerous gene regulatory networks. Here the authors demonstrate that miR-218 is an essential component of the gene regulatory network that controls motor neuron fate specification in the developing spinal cord.
- Karen P. Thiebes
- , Heejin Nam
- & Soo-Kyung Lee
-
Article |
MicroRNA-431 accelerates muscle regeneration and ameliorates muscular dystrophy by targeting Pax7 in mice
Skeletal muscle stem cells (satellite cells) express different levels of a critical transcriptional regulator Pax7. Here, the authors show that miR-431 regulates Pax7 levels in satellite cells of the developing and regenerating muscle, and that increased miR-431expression in these cells alleviates symptoms of muscular dystrophy in mice.
- Rimao Wu
- , Hu Li
- & Dahai Zhu