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https://www.readbyqxmd.com/read/29236960/microrna-128-3p-mediated-depletion-of-drosha-promotes-lung-cancer-cell-migration
#1
Tania Frixa, Andrea Sacconi, Mario Cioce, Giuseppe Roscilli, Fabiana Fosca Ferrara, Luigi Aurisicchio, Claudio Pulito, Stefano Telera, Maria Antonia Carosi, Paola Muti, Sabrina Strano, Sara Donzelli, Giovanni Blandino
Alteration in microRNAs (miRNAs) expression is a frequent finding in human cancers. In particular, widespread miRNAs down-regulation is a hallmark of malignant transformation. In the present report, we showed that the miR-128-3p, which is up-regulated in lung cancer tissues, has Drosha and Dicer, two key enzymes of miRNAs processing, as the main modulation targets leading to the widespread down-regulation of miRNA expression. We observed that the miRNAs downregulation induced by miR-128-3p contributed to the tumorigenic properties of lung cancer cells...
December 11, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29233865/dicer-and-mmset-catalyzed-h4k20me2-recruits-the-nucleotide-excision-repair-factor-xpa-to-dna-damage-sites
#2
Shalaka Chitale, Holger Richly
Ultraviolet (UV) irradiation triggers the recruitment of DNA repair factors to the lesion sites and the deposition of histone marks as part of the DNA damage response. The major DNA repair pathway removing DNA lesions caused by exposure to UV light is nucleotide excision repair (NER). We have previously demonstrated that the endoribonuclease DICER facilitates chromatin decondensation during lesion recognition in the global-genomic branch of NER. Here, we report that DICER mediates the recruitment of the methyltransferase MMSET to the DNA damage site...
December 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29226993/genetic-polymorphisms-of-microrna-machinery-genes-predict-overall-survival-of-esophageal-squamous-carcinoma
#3
Cuiju Wang, Hailing Dong, Haiyan Fan, Jianhua Wu, Guiying Wang
BACKGROUND: MicroRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) in miRNA processing machinery genes are implicated in carcinogenesis, as they change the expression profiles of miRNA. Six miR-SNPs in miRNA processing machinery genes, including Dicer (rs3742330), RAN (rs14035), XPO5 (rs11077), TNRC6B (rs9623117), GEMIN3 (rs197412), and GEMIN4 (rs2740348), were evaluated for their association with esophageal squamous cell carcinoma (ESCC). METHODS: The miR-SNP of the miRNA processing genes were genotyped using the polymerase chain reaction-ligase detection reaction (PCR-LDR) assay, while the XPO5 expression levels in ESCC tissues were measured by immunochemistry methods...
December 11, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29216900/treatment-with-a-dna-methyltransferase-inhibitor-feminizes-zebrafish-and-induces-long-term-expression-changes-in-the-gonads
#4
Laia Ribas, Konstantinos Vanezis, Marco Antonio Imués, Francesc Piferrer
BACKGROUND: The role of epigenetic modifications such as DNA methylation during vertebrate sexual development is far from being clear. Using the zebrafish model, we tested the effects of one of the most common DNA methyltransferase (dnmt) inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), which is approved for the treatment of acute myeloid leukaemia and is under active investigation for the treatment of solid tumours. Several dose-response experiments were carried out during two periods, including not only the very first days of development (0-6 days post-fertilization, dpf), as done in previous studies, but also, and as a novelty, the period of gonadal development (10-30 dpf)...
December 8, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29199004/dicer-reprograms-stromal-fibroblasts-to-a-pro-inflammatory-and-tumor-promoting-phenotype-in-ovarian-cancer
#5
Zongyuan Yang, Ping Jin, Sen Xu, Taoran Zhang, Xin Yang, Xiaoting Li, Xiao Wei, Chaoyang Sun, Gang Chen, Ding Ma, Qinglei Gao
Inflammation and host stromal activation contribute significantly to ovarian cancer (OC) initiation and malignant progression. However, the complex reciprocal interactions between them are largely unknown. Here, we discovered that the tumor suppressor gene Dicer was paradoxically overexpressed in ovarian tumor stroma, and induced fibroblast activation and stromal inflammation. Dicer transformed normal fibroblasts to a carcinoma-associated fibroblast (CAF)-like state, which was morphologically spread out and functionally activated to fuel tumor invasion and metastasis...
November 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29195056/rna-interference-mediated-gene-silencing-by-branched-tripodal-rnas-does-not-require-dicer-processing
#6
Yanghee Kim, Young Gyu Kang, Jeong Yong Choe, Dooyoung Lee, Chanseok Shin, Sun Woo Hong, Dong-Ki Lee
Specific gene silencing through RNA interference (RNAi) holds great promise as the next-generation therapeutic development platform. Previously, we have shown that branched, tripodal interfering RNA (tiRNA) structures could simultaneously trigger RNAi-mediated gene silencing of three target genes with 38 nt-long guide strands associated with Argonaute 2. Herein, we show that the branched RNA structure can trigger effective gene silencing in Dicer knockout cell line, demonstrating that the Dicer-mediated processing is not required for tiRNA activity...
December 1, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29184028/identification-of-a-new-host-factor-required-for-antiviral-rnai-and-amplification-of-viral-sirnas
#7
Zhongxin Guo, Xian-Bing Wang, Ying Wang, Wan-Xiang Li, Amit Gal-On, Shou-Wei Ding
Small interfering RNAs (siRNAs) processed from virus-specific dsRNA direct antiviral RNA interference (RNAi) in diverse eukaryotic hosts. We have recently performed a sensitized genetic screen in Arabidopsis thaliana and identified two related phospholipid flippases required for antiviral RNAi and the amplification of virus-derived siRNAs by plant RNA-dependent RNA polymerase 1 (RDR1) and RDR6. Here we report the identification and cloning of ANTIVIRAL RNAI-DEFECTIVE 2 (AVI2) from the same genetic screen. AVI2 encodes a multi-span transmembrane protein broadly conserved in plants and animals with two homologous human proteins known as magnesium transporters...
November 28, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29170046/the-single-von-willebrand-factor-c-domain-protein-svc-coding-gene-is-not-involved-in-the-hymenoptaecin-upregulation-after-israeli-acute-paralysis-virus-iapv-injection-in-the-bumblebee-bombus-terrestris
#8
Haidong Wang, Guy Smagghe, Ivan Meeus
Within insects, inductions of anti-microbial peptides (AMPs) have been reported after different virus challenges. It is believed that this link is not directly induced by the virus itself, but rather indirectly induced by secondary effects of virus infection. Here we explored if direct sensing of the virus could trigger AMP expression. Recently, a cytokine-like molecule vago, a member of the Single von Willebrand factor C-domain (SVC) protein family, has been shown to be induced by virus infection in a Dicer-2 dependent manner...
November 20, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29164620/repair-gene-mgmt-is-controlled-by-sp1-and-upregulated-by-glucocorticoids-but-not-by-temozolomide-and-radiation
#9
Dorthe Aasland, Thomas R Reich, Maja T Tomicic, Olivier J Switzeny, Bernd Kaina, Markus Christmann
Therapy of malignant glioma relies on treatment with the O(6) -methylating agent temozolomide (TMZ) concomitant with ionizing radiation followed by adjuvant TMZ. For the treatment of recurrences DNA chloroethylating drugs are also used. The main killing lesion induced by these drugs is O(6) -alkylguanine. Since this damage is repaired by O(6) -methylguanine-DNA methyltransferase (MGMT), the repair enzyme represents the most important factor of drug resistance, limiting the therapy of malignant high-grade gliomas...
November 22, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29159954/unraveling-the-mechanistic-complexity-of-the-glomerulocystic-phenotype-in-dicer-conditional-ko-mice-by-2d-gel-electrophoresis-coupled-mass-spectrometry
#10
Claudia Vincenza Fiumara, Domenica Scumaci, Anna Iervolino, Angela Mena Perri, Antonio Concolino, Laura Tammè, Federica Petrillo, Giovambattista Capasso, Giovanni Cuda
PURPOSE: Dicer, an RNase III type endonuclease, is a key enzyme involved in miRNA biogenesis. It has been shown that this enzyme is essential for several aspects of postnatal kidney functions and homeostasis. In this study, we have examined conditional knockout (cKO) mice for Dicer in Pax8 (Paired-box gene 8) expressing cells to investigate the kidney protein profile. This specific model develops a glomerulocystic phenotype coupled with urinary concentration impairment, proteinuria and severe renal failure...
November 21, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29156806/association-between-snps-in-microrna-machinery-genes-and-gastric-cancer-susceptibility-invasion-and-metastasis-in-chinese-han-population
#11
Xingbo Song, Huiyu Zhong, Qian Wu, Minjin Wang, Juan Zhou, Yi Zhou, Xiaojun Lu, Binwu Ying
Objective: The present study investigates the influence of genetic variants in miRNA machinery genes (DROSHA, DICER, AGO1, and GEMIN4) on gastric cancer in Chinese Han population, further revealing the genetic mechanisms of gastric cancer occurrence and development. Methods: Genotyping of single nucleotide polymorphisms (SNPs) was performed in 628 patients with GC and 502 frequency-matched (age and gender) controls by the high resolution melting (HRM) method. Results: The SNPs rs3742330 (DICER) and rs7813 (GEMIN4) were associated with susceptibility to gastric cancer (P = 0...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150673/m%C3%A3-ller-glial-micrornas-are-required-for-the-maintenance-of-glial-homeostasis-and-retinal-architecture
#12
Stefanie G Wohl, Nikolas L Jorstad, Edward M Levine, Thomas A Reh
To better understand the roles of microRNAs in glial function, we used a conditional deletion of Dicer1 (Dicer-CKOMG) in retinal Müller glia (MG). Dicer1 deletion from the MG leads to an abnormal migration of the cells as early as 1 month after the deletion. By 6 months after Dicer1 deletion, the MG form large aggregations and severely disrupt normal retinal architecture and function. The most highly upregulated gene in the Dicer-CKOMG MG is the proteoglycan Brevican (Bcan) and overexpression of Bcan results in similar aggregations of the MG in wild-type retina...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29141234/elevated-p53-activities-restrict-differentiation-potential-of-microrna-deficient-pluripotent-stem-cells
#13
Zhong Liu, Cheng Zhang, Maria Skamagki, Alireza Khodadadi-Jamayran, Wei Zhang, Dexin Kong, Chia-Wei Chang, Jingyang Feng, Xiaosi Han, Tim M Townes, Hu Li, Kitai Kim, Rui Zhao
Pluripotent stem cells (PSCs) deficient for microRNAs (miRNAs), such as Dgcr8(-/-) or Dicer(-/-) embryonic stem cells (ESCs), contain no mature miRNA and cannot differentiate into somatic cells. How miRNA deficiency causes differentiation defects remains poorly understood. Here, we report that miR-302 is sufficient to enable neural differentiation of differentiation-incompetent Dgcr8(-/-) ESCs. Our data showed that miR-302 directly suppresses the tumor suppressor p53, which is modestly upregulated in Dgcr8(-/-) ESCs and serves as a barrier restricting neural differentiation...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29141205/investigation-of-alimentary-canal-ultrastructure-following-knockdown-of-the-dicer-2-gene-in-planthoppers-reveals-the-potential-pathogenicity-of-southern-rice-black-streaked-dwarf-virus-to-its-insect-vector
#14
Yuyan Liu, Qianzhuo Mao, Hanhong Lan, Haitao Wang, Taiyun Wei, Qian Chen
An increasing number of studies are suggesting that plant viruses, including southern rice black-streaked dwarf virus (SRBSDV), can adversely affect biological characteristics of insect vectors by unknown mechanisms. To study the adverse effect of SRBSDV at cellular level on the insect vector, we promoted viral infection by the disruption of the small interfering RNA (siRNA) pathway. The transmission electron microscopy was utilized to describe the ultrastructural changes that occurred in insects when the core component of the siRNA pathway, Dicer-2, was knocked down...
November 12, 2017: Virus Research
https://www.readbyqxmd.com/read/29140168/revisiting-the-roles-of-tobamovirus-replicase-complex-proteins-in-viral-replication-and-silencing-suppression
#15
Nachelli Malpica-López, Rajendran Rajeswaran, Daria Beknazariants, Jonathan Seguin, Victor Golyaev, Laurent Farinelli, Mikhail M Pooggin
Tobamoviral replicase possesses an RNA-dependent RNA polymerase (RDR) domain and is translated from genomic (g)RNA via a stop codon readthrough mechanism at a one-to-ten ratio relative to a shorter protein lacking the RDR domain. The two proteins share methyltransferase and helicase domains and form a heterodimer implicated in gRNA replication. The shorter protein is also implicated in suppressing RNA silencing-based antiviral defenses. Using a stop codon mutant of Oilseed rape mosaic tobamovirus (ORMV), we demonstrate that the readthrough replicase (p182) is sufficient for gRNA replication and for subgenomic RNA transcription during systemic infection in Nicotiana benthamiana and Arabidopsis thaliana...
November 15, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/29133395/rna-stem-structure-governs-coupling-of-dicing-and-gene-silencing-in-rna-interference
#16
Hye Ran Koh, Amirhossein Ghanbariniaki, Sua Myong
PremicroRNAs (premiRNAs) possess secondary structures consisting of a loop and a stem with multiple mismatches. Despite the well-characterized RNAi pathway, how the structural features of premiRNA contribute to dicing and subsequent gene-silencing efficiency remains unclear. Using single-molecule FISH, we demonstrate that cytoplasmic mRNA, but not nuclear mRNA, is reduced during RNAi. The dicing rate and silencing efficiency both increase in a correlated manner as a function of the loop length. In contrast, mismatches in the stem drastically diminish the silencing efficiency without impacting the dicing rate...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29132690/cyclin-dependent-kinase-5-regulates-mapk-erk-signaling-in-the-skin-of-mice
#17
Xuexian Liu, Pengqian Zhang, Kaiyuan Ji, Junzhen Zhang, Shanshan Yang, Bin Du, Shuaipeng Hu, Ruiwen Fan
Cyclin-dependent kinase 5 (CDK5) is a proline-directed serine/threonine kinase that has been shown to play important roles in many tissues except the nervous system. We previously reported that CDK5 showed differential expression in the transcriptome profiles of the skin of alpacas with different hair colors. To understand the functional role of CDK5 in hair color determination, we constructed CDK5-knockdown mice and identified the effect on the mitogen-activated protein kinase (MAPK) pathway in the mouse skin...
November 11, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/29124087/annotating-and-quantifying-pri-mirna-transcripts-using-rna-seq-data-of-wild-type-and-serrate-1-globular-stage-embryos-of-arabidopsis-thaliana
#18
Daniel Lepe-Soltero, Alma Armenta-Medina, Daoquan Xiang, Raju Datla, C Stewart Gillmor, Cei Abreu-Goodger
The genome annotation for the model plant Arabidopsis thaliana does not include the primary transcripts from which MIRNAs are processed. Here we present and analyze the raw mRNA sequencing data from wild type and serrate-1 globular stage embryos of A. thaliana, ecotype Columbia. Because SERRATE is required for pri-miRNA processing, these precursors accumulate in serrate-1 mutants, facilitating their detection using standard RNA-Seq protocols. We first use the mapping of the RNA-Seq reads to the reference genome to annotate the potential primary transcripts of MIRNAs expressed in the embryo...
December 2017: Data in Brief
https://www.readbyqxmd.com/read/29117535/rescuing-infusion-of-mirna-1-prevents-cardiac-remodeling-in-a-heart-selective-mirna-deficient-mouse
#19
Shuilian Luo, Yuhang Chen, Rui He, Yujun Shi, Li Su
OBJECTIVE: The decreased expression of muscle-specific microRNA-1 (miR-1) has been found in many cardiovascular diseases and is considered to contribute to heart failure (HF). Here we investigated the role of miR-1 in myocardium protection by infusion of miR-1 in a cardiac global miRNA-deficient mouse. METHODS: We generated a cardiac-selective miRNA-deficient mouse by crossing Dicer(flox/flox) mice with mice expressing tamoxifen-inducible Cre recombinase under the control of a mouse αMHC promoter...
November 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29106606/increased-affinity-for-rna-targets-evolved-early-in-animal-and-plant-dicer-lineages-through-different-structural-mechanisms
#20
Haiyan Jia, Oralia Kolaczkowski, James Rolland, Bryan Kolaczkowski
Understanding the structural basis for evolutionary changes in protein function is central to molecular evolutionary biology and can help determine the extent to which functional convergence occurs through similar or different structural mechanisms. Here, we combine ancestral sequence reconstruction with functional characterization and structural modeling to directly examine the evolution of sequence-structure-function across the early differentiation of animal and plant Dicer/DCL proteins, which perform the first molecular step in RNA interference by identifying target RNAs and processing them into short interfering products...
July 5, 2017: Molecular Biology and Evolution
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