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https://www.readbyqxmd.com/read/29346554/functional-roles-of-sex-biased-growth-hormone-regulated-micrornas-mir-1948-and-mir-802-in-young-adult-mouse-liver
#1
Pengying Hao, David J Waxman
Sex-specific temporal patterns of pituitary GH secretion determine the sex-biased transcription of hundreds of genes in the liver and impart significant sex differences in liver physiology, metabolism and disease. Sex differences in hepatic gene expression vary widely, ranging from <2-fold to >1,000-fold in the mouse. Here, we use small RNA sequencing to discover 24 sex-biased mouse liver miRNAs, and then investigate the roles of two of these miRNAs in GH-regulated liver sex differences. Studies in pre-pubertal and young adult mice, and in mice where pituitary hormones are ablated or where sex-specific hepatic GH signaling is dysregulated, demonstrated that the male-biased miR-1948 and the female-biased miR-802 are both regulated by sex-specific pituitary GH secretory patterns, acquire sex specificity at puberty, and are dependent on the GH-activated transcription factor STAT5 for their sex-specific expression...
January 16, 2018: Endocrinology
https://www.readbyqxmd.com/read/29339534/inactivating-mutations-in-drosha-mediate-vascular-abnormalities-similar-to-hereditary-hemorrhagic-telangiectasia
#2
Xuan Jiang, Whitney L Wooderchak-Donahue, Jamie McDonald, Prajakta Ghatpande, Mai Baalbaki, Melissa Sandoval, Daniel Hart, Hilary Clay, Shaun Coughlin, Giorgio Lagna, Pinar Bayrak-Toydemir, Akiko Hata
The transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) family of cytokines critically regulates vascular morphogenesis and homeostasis. Impairment of TGF-β or BMP signaling leads to heritable vascular disorders, including hereditary hemorrhagic telangiectasia (HHT). Drosha, a key enzyme for microRNA (miRNA) biogenesis, also regulates the TGF-β and BMP pathway through interaction with Smads and their joint control of gene expression through miRNAs. We report that mice lacking Drosha in the vascular endothelium developed a vascular phenotype resembling HHT that included dilated and disorganized vasculature, arteriovenous fistulae, and hemorrhages...
January 16, 2018: Science Signaling
https://www.readbyqxmd.com/read/29335523/mir-139-5p-inhibits-aerobic-glycolysis-cell-proliferation-migration-and-invasion-in-hepatocellular-carcinoma-via-a-reciprocal-regulatory-interaction-with-ets1
#3
Shengni Hua, Ling Lei, Ling Deng, Xie Weng, Chengdong Liu, Xiaolong Qi, Shuang Wang, Dongyan Zhang, Xuejing Zou, Chuanhui Cao, Li Liu, Dehua Wu
Cancer cells have metabolic features that allow them to preferentially metabolize glucose through aerobic glycolysis, providing them with a progression advantage. However, microRNA (miRNA) regulation of aerobic glycolysis in cancer cells has not been extensively investigated. We addressed this in the present study by examining the regulation of miR-139-5p on aerobic glycolysis of hepatocellular carcinoma (HCC) using clinical specimens, HCC cells, and a mouse xenograft model. We found that overexpressing miR-139-5p restrained aerobic glycolysis, suppressing proliferation, migration, and invasion in HCC cells...
January 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29333004/drosha-rs642321-polymorphism-influence-susceptibility-to-childhood-acute-lymphoblastic-leukemia-a-preliminary-report
#4
Mohammad Hashemi, Seyed-Shahaboddin Hasani, Majid Naderi
Introduction: It has been well known that the microRNA biogenesis is involved in the pathogenesis of various diseases. We investigated the possible association between DROSHA rs642321 variant and risk of acute lymphocytic leukemia (ALL). Materials and Methods: We genotyped 75 children diagnosed with ALL and 115 age- and sex-matched children with no history of cancer of any type (as the control group) by the tetra amplification refractory mutation system-polymerase chain reaction...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29260525/-the-association-between-the-polymorphisms-of-mirna-biogenesis-related-genes-dicer-drosha-and-ran-and-unexplained-recurrent-spontaneous-abortion-in-chinese-women
#5
Mei Fu, Wen-Ming Xu, Tai-Zhou Qin, Ke-Hui Xu
OBJECTIVE: To explore the association between polymorphisms of miRNA biogenesis related gene DICER,DROSHA,RAN and unexplained recurrent spontaneous abortion (URSA) in Chinese women. METHODS: We recruited 217 patients with URSA (URSA group) and 390 healthy controls who were fertile women with history of more than one successful pregnancy outcome (control group) from June 2013 to December 2015 in the West China Second University Hospital of Sichuan University. The control group was recruited from regular physical examination and prepregnancy check for women of childbearing age during the same period...
November 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/29236960/microrna-128-3p-mediated-depletion-of-drosha-promotes-lung-cancer-cell-migration
#6
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/29187591/microrna-dynamics-at-the-onset-of-primordial-germ-and-somatic-cells-sex-differentiation-during-mouse-embryonic-gonad-development
#7
Daniel Fernandez-Perez, Miguel Angel Brieño-Enriquez, Javier Isoler-Alcaraz, Eduardo Larriba, Jesus Del Mazo
IIn mammals, commitment and specification of germ cell lines implies involves complex programs that include sex differentiation, control of proliferation and meiotic initiation. Regulation of these processes is genetically controlled by fine-tuned mechanisms of gene regulation in which microRNAs (miRNAs) are involved. We have characterized, by small-RNAseq and bioinformatics analyses, the miRNA expression patterns of male and female mouse Primordial Germ Cells (PGCs) and gonadal somatic cells at embryonic stages: E11...
November 29, 2017: RNA
https://www.readbyqxmd.com/read/29171334/g-quadruplexes-influence-pri-microrna-processing
#8
Samuel G Rouleau, Jean-Michel Garant, François Bolduc, Martin Bisaillon, Jean-Pierre Perreault
RNA G-Quadruplexes (G4) have been shown to possess many biological functions, including the regulation of microRNA (miRNA) biogenesis and function. However, their impact on pri-miRNA processing remains unknown. We identified G4 located near the Drosha cleavage site in three distinct pri-miRNAs: pri-mir200c, pri-mir451a, and pri-mir497. The folding of the potential G4 motifs was determined in solution. Subsequently, mutations disrupting G4 folding led to important changes in the mature miRNAs levels in cells...
December 11, 2017: RNA Biology
https://www.readbyqxmd.com/read/29171328/emerging-roles-of-drosha-beyond-primary-microrna-processing
#9
Dooyoung Lee, Chanseok Shin
DROSHA is the catalytic subunit of the Microprocessor complex, which initiates microRNA (miRNA) maturation in the nucleus by recognizing and cleaving hairpin precursors embedded in primary transcripts. However, accumulating evidence suggests that not all hairpin substrates of DROSHA are associated with the generation of functional small RNAs. By targeting those hairpins, DROSHA regulates diverse aspects of RNA metabolism across the transcriptome, serves as a line of defense against the expression of potentially deleterious elements, and permits cell fate determination and differentiation...
November 24, 2017: RNA Biology
https://www.readbyqxmd.com/read/29170488/heme-enables-proper-positioning-of-drosha-and-dgcr8-on-primary-micrornas
#10
Alexander C Partin, Tri D Ngo, Emily Herrell, Byung-Cheon Jeong, Gary Hon, Yunsun Nam
MicroRNAs regulate the expression of many proteins and require specific maturation steps. Primary microRNA transcripts (pri-miRs) are cleaved by Microprocessor, a complex containing the RNase Drosha and its partner protein, DGCR8. Although DGCR8 is known to bind heme, the molecular role of heme in pri-miR processing is unknown. Here we show that heme is critical for Microprocessor to process pri-miRs with high fidelity. Furthermore, the degree of inherent heme dependence varies for different pri-miRs. Heme-dependent pri-miRs fail to properly recruit Drosha, but heme-bound DGCR8 can correct erroneous binding events...
November 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29157048/the-drosha-rs10719-t-c-polymorphism-is-associated-with-preeclampsia-susceptibility
#11
Mahnaz Rezaei, Fatemeh Eskandari, Abbas Mohammadpour-Gharehbagh, Batool Teimoori, Minoo Yaghmaei, Mojgan Mokhtari, Saeedeh Salimi
PURPOSE: Drosha is a member of the micro RNA (miRNA) processing machinery that affects miRNA processing. Single-nucleotide polymorphisms (SNPs) in the Drosha gene might affect microRNA processing and the expression of various genes. The aim of this study is to investigate the association between SNPs in the Drosha gene and preeclampsia (PE) in the southeast of Iran. METHODS: Genotyping of Drosha rs10719 and rs6877842 was performed using blood samples from 219 PE women and 205 healthy control subjects by a polymerase chain reaction-restriction fragment length polymorphism method...
November 20, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29156806/association-between-snps-in-microrna-machinery-genes-and-gastric-cancer-susceptibility-invasion-and-metastasis-in-chinese-han-population
#12
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/29109067/the-insertion-in-the-double-stranded-rna-binding-domain-of-human-drosha-is-important-for-its-function
#13
Xiaoxiao Zhang, Peng Li, Jian Lin, Haochu Huang, Bin Yin, Yan Zeng
microRNAs (miRNAs) are first transcribed as long, primary transcripts, which are then processed by multiple enzymes and proteins to generate the single-stranded, approximately 22-nucleotide (nt)-long mature miRNAs. A critical step in animal miRNA biogenesis is the cleavage of primary miRNA transcripts (pri-miRNAs) to produce precursor miRNAs (pre-miRNAs) by the enzyme Drosha. How Drosha recognizes its substrates remains incompletely understood. In this study we constructed a series of human Drosha mutants and examined their enzymatic activities and interaction with RNAs...
November 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29084369/bleomycin-can-cleave-an-oncogenic-non-coding-rna
#14
Matthew Disney, Alicia Angelbello
Non-coding RNAs are pervasive in cells and contribute to diseases such as cancer. A question in biomedical research is if non-coding RNAs are targets of medicines. Bleomycin is a natural product that cleaves DNA, however, it is known to cleave RNA in vitro. Herein, an in-depth analysis of the RNA cleavage preferences of bleomycin A5 is presented. Bleomycin A5 prefers to cleave RNAs with stretches of AU base pairs. Based on these preferences and a bioinformatic analysis, the microRNA10b hairpin precursor was identified as a potential substrate for bleomycin A5...
October 30, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29063830/many-si-shrnas-can-kill-cancer-cells-by-targeting-multiple-survival-genes-through-an-off-target-mechanism
#15
William Putzbach, Quan Q Gao, Monal Patel, Stijn van Dongen, Ashley Haluck-Kangas, Aishe A Sarshad, Elizabeth T Bartom, Kwang-Youn A Kim, Denise M Scholtens, Markus Hafner, Jonathan C Zhao, Andrea E Murmann, Marcus E Peter
Over 80% of multiple-tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death characterized by simultaneous activation of multiple cell death pathways preferentially killing transformed and cancer stem cells. We now show these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3'UTR of critical survival genes in a unique form of off-target effect we call DISE (death induced by survival gene elimination). Drosha and Dicer-deficient cells, devoid of most miRNAs, are hypersensitive to DISE, suggesting cellular miRNAs protect cells from this form of cell death...
October 24, 2017: ELife
https://www.readbyqxmd.com/read/29056292/epigenetics-and-gene-expression-profile-in-first-episode-psychosis-the-role-of-childhood-trauma
#16
REVIEW
Simona Tomassi, Sarah Tosato
Childhood Trauma (CT) mediation of the epigenome and its impact on gene expression profile could provide a mechanism for the gene-environment interaction underling psychosis. We reviewed the evidence concerning epigenetic and gene expression modifications associated with CT in both First-Episode Psychosis (FEP) and healthy subjects. In order to explore the relative role of psychosis itself in determining these modifications, evidence about FEP and epigenetics/gene expression was also summarized. We performed a systematic search on PubMed, last updated in December 2016...
October 19, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29053842/differential-expression-of-water-channel-and-noncoding-rna-biogenesis-related-genes-in-three-lines-of-chickens-under-a-short-term-water-restriction
#17
S Orlowski, J Flees, N Anthony, S Dridi
Genetic selection for high growth rate has resulted in tremendous changes not only in feed efficiency, but also in water consumption between modern broilers and their ancestor jungle fowl (JF). However molecular mechanisms involved in water homeostasis are still not well defined. This study aimed, therefore, to determine the effect of short-term water restriction on the expression of water channel- and noncoding RNA biogenesis-related genes in the kidney and whole blood of JF, broiler population from the 1990s (RB1995), and modern broiler population developed in 2015 (ARB2015)...
October 5, 2017: Poultry Science
https://www.readbyqxmd.com/read/29042235/splicing-factors-as-regulators-of-mirna-biogenesis-links-to-human-disease
#18
REVIEW
Madara Ratnadiwakara, Monika Mohenska, Minna-Liisa Änkö
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally by fine-tuning mRNA levels and translation during development and in adult tissues. miRNAs are transcribed as parts of longer precursors that undergo multiple processing steps before the mature miRNAs reach their target mRNAs in the cytoplasm. In addition to Drosha/DGCR8 and Dicer that are the essential components of the miRNA processing pathway, a range of other RNA binding proteins have recently been implicated in miRNA biogenesis...
October 19, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29036314/mirnovo-genome-free-prediction-of-micrornas-from-small-rna-sequencing-data-and-single-cells-using-decision-forests
#19
Dimitrios M Vitsios, Elissavet Kentepozidou, Leonor Quintais, Elia Benito-Gutiérrez, Stijn van Dongen, Matthew P Davis, Anton J Enright
The discovery of microRNAs (miRNAs) remains an important problem, particularly given the growth of high-throughput sequencing, cell sorting and single cell biology. While a large number of miRNAs have already been annotated, there may well be large numbers of miRNAs that are expressed in very particular cell types and remain elusive. Sequencing allows us to quickly and accurately identify the expression of known miRNAs from small RNA-Seq data. The biogenesis of miRNAs leads to very specific characteristics observed in their sequences...
September 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29020972/sumo1-modification-of-khsrp-regulates-tumorigenesis-by-preventing-the-tl-g-rich-mirna-biogenesis
#20
Haihua Yuan, Rong Deng, Xian Zhao, Ran Chen, Guofang Hou, Hailong Zhang, Yanli Wang, Ming Xu, Bin Jiang, Jianxiu Yu
BACKGROUND: MicroRNAs (miRNAs) are important regulators involved in diverse physiological and pathological processes including cancer. SUMO (small ubiquitin-like modifier) is a reversible protein modifier. We recently found that SUMOylation of TARBP2 and DGCR8 is involved in the regulation of the miRNA pathway. KHSRP is a single stranded nucleic acid binding protein with roles in transcription and mRNA decay, and it is also a component of the Drosha-DGCR8 complex promoting the miRNA biogenesis...
October 11, 2017: Molecular Cancer
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