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| Open AccessSumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs
Cells secrete micro-RNAs by packaging them into exosomes; however, the mechanisms by which this packaging occurs are unclear. Here, the authors identify a sequence motif that confers exosomal targeting to micro-RNAs and identify a ribonucleoprotein complex that plays a role in this process.
- Carolina Villarroya-Beltri
- , Cristina Gutiérrez-Vázquez
- & Francisco Sánchez-Madrid
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The atypical mechanosensitive microRNA-712 derived from pre-ribosomal RNA induces endothelial inflammation and atherosclerosis
Gene expression in the vascular endothelium is sensitive to shear forces exerted by the circulation. Here the authors identify miR-712 as a mechanosensitive microRNA expressed in endothelial cells and show that miR-712 inhibits pro-atherogenic processes by downregulating tissue inhibitor of metalloproteinase 3.
- Dong Ju Son
- , Sandeep Kumar
- & Hanjoong Jo
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| Open AccessmiRNomes of haematopoietic stem cells and dendritic cells identify miR-30b as a regulator of Notch1
Several microRNAs have been implicated in the differentiation of immune cells. Here the authors analyse the global microRNA expression profiles of mouse haematopoietic stem cells and different stages of dendritic cell development and identify Notch1 as a target of miR-30b in regulatory dendritic cells.
- Xiaoping Su
- , Cheng Qian
- & Xuetao Cao
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| Open AccessMicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice
The micro-RNA miR-33 is encoded by an intron of the gene encoding sterol regulatory-binding protein 2 (SREBP-2) and controls cholesterol homoeostasis. Here, Horie et al.identify SREBP-1 as a target of miR-33 and show that deletion of miR-33 promotes diet-induced obesity and liver steatosis in mice.
- Takahiro Horie
- , Tomohiro Nishino
- & Koh Ono
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Cyclin D1 induction of Dicer governs microRNA processing and expression in breast cancer
Whether microRNA processing mediated by Dicer is regulated in a cell-cycle-dependent manner is unknown. Here, Chen et al.show that Cyclin D1, which is important in the control of the cell cycle, regulates the expression of Dicer, and that Cyclin D1 and Dicer expression levels correlate in breast cancer.
- Zuoren Yu
- , Liping Wang
- & Richard G. Pestell
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miR-1 and miR-206 target different genes to have opposing roles during angiogenesis in zebrafish embryos
The microRNAs miR-1 and miR-206 have identical seed sequences and have been reported to regulate angiogenesis in zebrafish by repressing VegfAa expression. Here, Lin et al.describe opposing roles of the two microRNAs in regulating VegfAa expression and therefore angiogenesis in zebrafish.
- Cheng-Yung Lin
- , Hung-Chieh Lee
- & Huai-Jen Tsai
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| Open AccessIdentification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif
AGO-CLIP permits the identification of miRNA target genes. Here, Hamilton et al. compile publicly available AGO-CLIP data and combine this information with miRNA analysis from The Cancer Genome Atlas, permitting the identification of an oncogenic miRNA superfamily that targets tumour suppressor genes.
- Mark P. Hamilton
- , Kimal Rajapakshe
- & Sean E. McGuire
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miRNAs confer phenotypic robustness to gene networks by suppressing biological noise
MicroRNAs are thought to confer robustness to biological processes, but clear experimental evidence is still needed. Here, Siciliano et al. construct a toggle-switch in mammalian cells to show that microRNAs buffer fluctuations in protein levels, thereby providing phenotypic robustness to gene regulatory networks.
- Velia Siciliano
- , Immacolata Garzilli
- & Diego di Bernardo
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Tumour angiogenesis regulation by the miR-200 family
The microRNA-200 family members have a role in regulating tumour angiogenesis but the underlying mechanism is unclear. In this study, Pecot et al.demonstrate that miR-200 affects angiogenesis by altering endothelial and cancer cell cytokine secretion.
- Chad V. Pecot
- , Rajesha Rupaimoole
- & Anil K. Sood
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The effects of carbon dioxide and temperature on microRNA expression in Arabidopsis development
An increase in the concentration of atmospheric carbon dioxide and warmer temperatures can alter plant growth and development. Here the authors show that these conditions can also elicit significant changes in microRNAs expression, including some which might induce early flowering in Arabidopsis.
- Patrick May
- , Will Liao
- & Qiong A. Liu
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Disparity between microRNA levels and promoter strength is associated with initiation rate and Pol II pausing
MicroRNAs are known to be transcribed by RNA polymerase II. The authors show that microRNA promoters driven by TATA-box or NF-κB have increased rates of transcription re-initiation, which leads to local crowding of RNA polymerase II and lower efficiency of microRNA synthesis.
- Nadav Marbach-Bar
- , Amitai Ben-Noon
- & Rivka Dikstein
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| Open AccessHaemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21
microRNAs rapidly regulate gene expression and are implicated in cardiogenesis and angiogenesis. Banjo and colleagues show that the microRNA mir-21 is activated by the physical forces generated by blood flow, and that this regulates the development of heart valves in zebrafish.
- Toshihiro Banjo
- , Janin Grajcarek
- & Toshihiko Ogura
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MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1
Lung cancers have a high potential to become metastatic, which is a major cause of treatment failure. Here, the authors identify a microRNA that is upregulated in non-small-cell lung cancer and is associated with Hippo pathway modulation metastasis and poor clinical outcome.
- Ching-Wen Lin
- , Yih-Leong Chang
- & Pan-Chyr Yang
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Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9
Microglia are specialized immune cells in the brain. Here Åkerblom and colleagues use a microRNA-9-regulated lentiviral vector for the targeted genetic modification of microglia in the rodent brain, presenting a tool that may facilitate functional studies of resident microglia.
- Malin Åkerblom
- , Rohit Sachdeva
- & Johan Jakobsson
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| Open AccessmiR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit
Brown fat can dissipate energy as heat and has an important role in energy homoeostasis of rodents and possibly humans. Chenet al. show that microRNA 155 regulates the differentiation of brown adipocytes as well as the 'browning' of white fat cells in mice.
- Yong Chen
- , Franziska Siegel
- & Alexander Pfeifer
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MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11
The role of microRNAs in chemotherapy resistance remains to be elucidated. Bockhorn et al.report that microRNA-30c, a human breast tumour prognostic marker, has a key role by targeting the epithelial-to-mesenchymal transition promoter twinfilin 1 and downstream interleukin-11 expression.
- Jessica Bockhorn
- , Rachel Dalton
- & Huiping Liu
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Elevated oncofoetal miR-17-5p expression regulates colorectal cancer progression by repressing its target gene P130
Tumorigenesis has been likened to a form of cellular reversion to the embryonic state. Ma et al.identify a foetal miRNA as an oncogenic activator of the Wnt/β-catenin pathway in colorectal cancer, whose expression is negatively correlated with survival but is positively correlated with response to adjuvant chemotherapy.
- Yanlei Ma
- , Peng Zhang
- & Huanlong Qin
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| Open AccessEvolution of the human-specific microRNA miR-941
miRNAs simultaneously regulate a range of genes, making them potential master players in evolution. Huet al.identify a human-specific miRNA called miR-941, whose copy number remains polymorphic in modern humans, and show that miR-941 is expressed in the brain and could regulate important signalling pathways.
- Hai Yang Hu
- , Liu He
- & Philipp Khaitovich
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| Open AccessThe miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy
Heart failure is often a consequence of pathological growth of cardiomyocytes or cardiac hypertrophy. Here Ucar and colleagues report that the microRNAs miR-132 and miR-212 promote cardiac hypertrophy and inhibit autophagy in cardiomyocytes by downregulating the transcription factor FoxO3.
- Ahmet Ucar
- , Shashi K. Gupta
- & Thomas Thum
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Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation
Embryonic stem cells have a shortened cell cycle that allows for rapid proliferation, but the exact mechanisms are unclear. Here, a microRNA target, Trim71, is shown to inhibit the expression of a cyclin-dependent kinase inhibitor, thus enabling the G1–S phase cell cycle transition in embryonic stem cells.
- Hao-Ming Chang
- , Natalia J. Martinez
- & Richard I. Gregory
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miR-484 regulates mitochondrial network through targeting Fis1
Abnormal mitochondrial fission leads to apoptosis and disease. Li and colleagues reveal the mechanism with which the transcription factor Foxo3a suppresses Fis1-mediated mitochondrial fission and apoptosis in cardiomyocytes and adrenocortical cancer cells, which involves miR-484 inhibition of Fis1 translation.
- Kun Wang
- , Bo Long
- & Pei-Feng Li
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miR-196b directly targets both HOXA9/MEIS1 oncogenes and FAS tumour suppressor in MLL-rearranged leukaemia
HOX9AandMEIS1are key oncogenes in MLL-rearranged leukaemia. miRNA-196b is shown here to directly suppress their expression and delay MLL-fusion-mediated leukaemia, but to also cause an aggressive leukaemia phenotype when expressed ectopically, suggesting that it targets tumour suppressors as well.
- Zejuan Li
- , Hao Huang
- & Jianjun Chen
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| Open AccessGenome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis
microRNAs are known to be deregulated in cancer. Using a screen for microRNAs that alter cell migration, Zhanget al. show that mir-23b blocks cell migration in vitro and in vivoand is reduced in expression in human colon cancer, suggesting a therapeutic potential for this microRNA.
- Hanshuo Zhang
- , Yang Hao
- & Jianzhong Jeff Xi
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miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells
The microRNA miR-137 is enriched in the brain of mice and induces the differentiation of adult neural stem cells. Now, Sun and colleagues report that miR-137 negatively regulates proliferation of neurons in embryonic mice and that TLX and LSD1 cooperate to negatively regulate miR-137 expression, blocking premature differentiation.
- GuoQiang Sun
- , Peng Ye
- & Yanhong Shi
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| Open AccessSelective inhibition of microRNA accessibility by RBM38 is required for p53 activity
MicroRNAs bind to the 3′-untranslated region of genes to regulate expression. In this study, an RNA-binding protein, RMB38, is shown to selectively regulate the access of some microRNAs to their targets, and control the expression of some p53 target genes.
- Nicolas Léveillé
- , Ran Elkon
- & Reuven Agami
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MicroRNA122 is a key regulator of α-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma
α-fetoprotein is used as a biomarker of hepatocellular cancer but the mechanisms that lead to its elevated expression are unknown. Kojimaet al.show that microRNA122 and CUX1 are important for the regulation of α-fetoprotein and suggest that loss of microRNA122 leads to more aggressive liver cancer.
- Kentaro Kojima
- , Akemi Takata
- & Kazuhiko Koike