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Shiqi Luo, Feng He, Junjie Luo, Shengqian Dou, Yirong Wang, Annan Guo, Jian Lu
Transfer RNA-derived small RNAs (tsRNAs) are an emerging class of small RNAs, yet their regulatory roles have not been well understood. Here we studied the molecular mechanisms and consequences of tsRNA-mediated regulation in Drosophila. By analyzing 495 public small RNA libraries, we demonstrate that most tsRNAs are conserved, prevalent and abundant in Drosophila. By carrying out mRNA sequencing and ribosome profiling of S2 cells transfected with single-stranded tsRNA mimics and mocks, we show that tsRNAs recognize target mRNAs through conserved complementary sequence matching and suppress target genes by translational inhibition...
March 14, 2018: Nucleic Acids Research
Bastian Ramms, Philip L S M Gordts
PURPOSE OF REVIEW: Apolipoprotein (apo) C-III is a key player in triglyceride-rich lipoprotein metabolism and strongly associated with elevated plasma triglyceride levels. Several new studies added important insights on apoC-III and its physiological function confirming its promise as a valid therapeutic target. RECENT FINDINGS: APOC3 is expressed in liver and intestine and regulates triglyceride-rich lipoprotein (TRL) catabolism and anabolism. The transcriptional regulation in both organs requires different regulatory elements...
March 15, 2018: Current Opinion in Lipidology
Shu Meng, Qilin Gu, Xiaojie Yang, Jie Lv, Iris Owusu, Gianfranco Matrone, Kaifu Chen, John P Cooke, Longhou Fang
Background -Angiogenesis is integral for embryogenesis, and targeting angiogenesis improves the outcome of many pathological conditions in patients. TBX20 is a crucial transcription factor for embryonic development, and its deficiency is associated with congenital heart disease. However, the role of TBX20 in angiogenesis has not been described. Methods -Loss- and gain-of-function approaches were used to explore the role of TBX20 in angiogenesis both in vitro and in vivo Angiogenesis gene array was used to identify key downstream targets of TBX20...
March 15, 2018: Circulation
Vesa M Olkkonen, Juha Sinisalo, Matti Jauhiainen
Remarkably good results have been achieved in the treatment of atherosclerotic cardiovascular diseases (CVD) by using statin, ezetimibe, antihypertensive, antithrombotic, and PCSK9 inhibitor therapies and their proper combinations. However, despite this success, the remaining CVD risk is still high. To target this residual risk and to treat patients who are statin-intolerant or have an exceptionally high CVD risk for instance due to familial hypercholesterolemia (FH), new therapies are intensively sought. One pathway of drug development is targeting the circulating triglyceride-rich lipoproteins (TRL) and their lipolytic remnants, which, according to the current view, confer a major CVD risk...
March 8, 2018: Atherosclerosis
Yufeng Du, Xiaoyan Hao, Xuejun Liu
The present study aimed to investigate the expression of long non-coding RNA (lncRNA) cyclin dependent kinase inhibitor-2B-antisense RNA 1 CDKN2B-AS1 in patients with peripheral blood of idiopathic pulmonary fibrosis (IPF). A total of 24 patients with IPF and 24 healthy controls were included in the study, four patients with IPF and four healthy controls were selected randomly to extract RNA. There were no other diseases such as hypertension and diabetes in the two groups. RNA from peripheral blood was extracted by high-throughput sequencing and bioinformatics analysis was performed...
April 2018: Oncology Letters
Zhihong Feng, Baolong Wang
Bladder cancer is among the most frequent types of genitourinary malignancies and results in high morbidity and mortality. Despite considerable progress in methods of bladder cancer diagnosis and treatment, the detailed underlying molecular mechanisms of bladder cancer remain unclear, and the prognosis of patients remains poor. In the present study, the role of long non-coding (lnc)RNA hepatocyte nuclear factor 1A (HNF1A)-antisense RNA (AS)1 in bladder cancer progression was examined in vitro . HNF1A-AS1 was overexpressed in clinical bladder cancer tissues and cultured bladder cancer cells...
April 2018: Oncology Letters
Shanshan Sun, Yansheng Wu, Wenyu Guo, Feng Yu, Lingping Kong, Yu Ren, Yu Wang, Xiaofeng Yao, Chao Jing, Chao Zhang, Mingyang Liu, Yuqing Zhang, Minghui Zhao, Zhaoqing Li, Chuanqiang Wu, Yu Qiao, Jingxuan Yang, Xudong Wang, Lun Zhang, Min Li, Xuan Zhou
PURPOSE: Phosphotidylinositol-3-kinase (PI3K)and signal transducers and activators of transcription 3 (STAT3) are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate HNSCC growth. The lncRNA HOX transcript antisense RNA (HOTAIR) was found to modulate the progression of head and neck squamous cell cancer (HNSCC). In this study, we attempted to establish the correlation of PI3K-STAT3-HOTAIR signaling with the progression of HNSCC and its sensitivity towards platinum-based and targeted anti-EGFR combination therapy...
March 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Aaron Balasingam Koenig, Juan Martín Barajas, María Jose Guerrero, Kalpana Ghoshal
MicroRNAs are ~22 nucleotide RNAs that regulate gene expression at the post-transcriptional level by binding messenger RNA transcripts. miR-21 is described as an oncomiR whose steady-state levels are commonly increased in many malignancies, including hepatocellular carcinoma (HCC). Methods known as cross-linking and immunoprecipitation of RNA followed by sequencing (CLIP-seq) have enabled transcriptome-wide identification of miRNA interactomes. In our study, we use a publicly available Argonaute-CLIP dataset (GSE97061), which contains nine HCC cases with matched benign livers, to characterize the miR-21 interactome in HCC...
March 14, 2018: International Journal of Molecular Sciences
Tomoya Maeda, Yuya Tanaka, Masayuki Inui
The Corynebacterium glutamicum R grtA (cgR_2936), grtB (cgR_2934), and grtC (cgR_2933) genes were identified as paralogs encoding glutamine-rich toxic proteins. We also identified a new antisense small RNA AsgR (antisense sRNA for grtA) that overlaps the 3' end of the grtA gene. Single over-expressions of grtA, grtB, and grtC resulted in complete inhibition of Escherichia coli cell growth. This growth was rescued by co-expression of AsgR. Similar effects were observed in C. glutamicum, although the toxicities of these proteins were moderate...
March 14, 2018: Molecular Microbiology
Magdalena Dabrowska, Wojciech Juzwa, Wlodzimierz J Krzyzosiak, Marta Olejniczak
Huntington's disease (HD) is a progressive autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in the first exon of the huntingtin gene ( HTT ). The accumulation of polyglutamine-rich huntingtin proteins affects various cellular functions and causes selective degeneration of neurons in the striatum. Therapeutic strategies used to date to silence the expression of mutant HTT include antisense oligonucleotides, RNA interference-based approaches and, recently, genome editing with the CRISPR/Cas9 system...
2018: Frontiers in Neuroscience
Uwe Wolfrum, Kerstin Nagel-Wolfrum
The human Usher syndrome (USH) is a complex, rare disease manifesting in its most common form of inherited deaf-blindness. Due to the heterogeneous manifestation of the clinical symptoms, three clinical types (USH1-3) are distinguished according to the severity of the disease pattern. For a correct diagnosis, in addition to the auditory tests in early newborn screening, ophthalmological examinations and molecular genetic analysis are important. Ten known USH genes encode proteins, which are from heterogeneous protein families, interact in functional protein networks...
March 2018: Klinische Monatsblätter Für Augenheilkunde
Xin Mu, Emily Greenwald, Sadeem Ahmad, Sun Hur
The emergence of RNA-based therapeutics demands robust and economical methods to produce RNA with few byproducts from aberrant activity. While in vitro transcription using the bacteriophage T7 RNA polymerase is one such popular method, its transcripts are known to display an immune-stimulatory activity that is often undesirable and uncontrollable. We here showed that the immune-stimulatory activity of T7 transcript is contributed by its aberrant activity to initiate transcription from a promoter-less DNA end...
March 9, 2018: Nucleic Acids Research
Tanmoy Mondal, Prasanna Kumar Juvvuna, Agnete Kirkeby, Sanhita Mitra, Subazini Thankaswamy Kosalai, Larissa Traxler, Falk Hertwig, Sara Wernig-Zorc, Caroline Miranda, Lily Deland, Ruth Volland, Christoph Bartenhagen, Deniz Bartsch, Sashidhar Bandaru, Anne Engesser, Santhilal Subhash, Tommy Martinsson, Helena Carén, Levent M Akyürek, Leo Kurian, Meena Kanduri, Maite Huarte, Per Kogner, Matthias Fischer, Chandrasekhar Kanduri
Trait-associated loci often map to genomic regions encoding long noncoding RNAs (lncRNAs), but the role of these lncRNAs in disease etiology is largely unexplored. We show that a pair of sense/antisense lncRNA (6p22lncRNAs) encoded by CASC15 and NBAT1 located at the neuroblastoma (NB) risk-associated 6p22.3 locus are tumor suppressors and show reduced expression in high-risk NBs. Loss of functional synergy between 6p22lncRNAs results in an undifferentiated state that is maintained by a gene-regulatory network, including SOX9 located on 17q, a region frequently gained in NB...
March 12, 2018: Cancer Cell
Shulin Fan, Chunni Fan, Ning Liu, Keke Huang, Xuedong Fang, Keren Wang
Long non-coding RNAs (lncRNAs) are non‑coding RNAs that are >200 nucleotides in length. Recent studies have identified a number of lncRNAs with critical roles in various biological processes including tumorigenesis. Zinc finger antisense 1 (ZFAS1) is a lncRNA that has recently been reported to be involved in the progression of several human cancers. However, the biological function of ZFAS1 in breast cancer remains to be elucidated. In order to determine the effect of ZFAS1 in breast cancer cells, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to measure ZFAS1 expression in cells from breast cancer cell lines...
March 9, 2018: Molecular Medicine Reports
Chao Li, Runchen Miao, Jingyao Zhang, Kai Qu, Chang Liu
Accumulating evidence highlights the fact that long non‑coding RNAs (lncRNAs) serve as critical factors in the growth of hepatocellular carcinoma (HCC). The dysregulation of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) has been reported in numerous human benign diseases. However, the role of KCNQ1OT1 in human HCC remains poorly understood. In this study, we demonstrated that the expression of KCNQ1OT1 was abnormally increased in HCC tissues. The ectopic high expression of KCNQ1OT1 was associated with liver cirrhosis, a larger tumor size, an advanced TNM stage, and a worse overall survival and tumor‑free survival...
March 12, 2018: International Journal of Oncology
Rintaro Iwata Hara, Yuki Hisada, Yusuke Maeda, Takanori Yokota, Takeshi Wada
Heteroduplex oligonucleotides (HDOs), composed of a DNA/LNA gapmer and its complementary RNA, are a novel, promising candidates for antisense drugs. We previously reported oligodiaminogalactoses (ODAGals), designed to bind to A-type nucleic acid duplexes such as DNA/RNA and RNA/RNA duplexes. In this paper, we report oligodiguanidinogalactoses (ODGGals) as novel A-type duplex binding molecules. We aimed to study in detail applicability of ODAGals and ODGGals for additives to HDOs as an antisense drug. The effect of ODAGal4 (ODAGal 4mer) and ODGGal3 (ODGGal 3mer) on an HDO were evaluated by UV melting analyses, RNA degradation study by ribonuclease A (RNase A), and ribonuclease H (RNase H)...
March 12, 2018: Scientific Reports
Hiroya Kuwahara, Jindong Song, Takahiro Shimoura, Kie Yoshida-Tanaka, Tadahaya Mizuno, Tatsuki Mochizuki, Satoshi Zeniya, Fuying Li, Kazutaka Nishina, Tetsuya Nagata, Shingo Ito, Hiroyuki Kusuhara, Takanori Yokota
The blood-brain barrier (BBB) is increasingly regarded as a dynamic interface that adapts to the needs of the brain, responds to physiological changes, and gets affected by and can even promote diseases. Modulation of BBB function at the molecular level in vivo is beneficial for a variety of basic and clinical studies. Here we show that our heteroduplex oligonucleotide (HDO), composed of an antisense oligonucleotide and its complementary RNA, conjugated to α-tocopherol as a delivery ligand, efficiently reduced the expression of organic anion transporter 3 (OAT3) gene in brain microvascular endothelial cells in mice...
March 12, 2018: Scientific Reports
Anna Maikova, Johann Peltier, Pierre Boudry, Eliane Hajnsdorf, Nicolas Kint, Marc Monot, Isabelle Poquet, Isabelle Martin-Verstraete, Bruno Dupuy, Olga Soutourina
Clostridium difficile, a major human enteropathogen, must cope with foreign DNA invaders and multiple stress factors inside the host. We have recently provided an experimental evidence of defensive function of the C. difficile CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system important for its survival within phage-rich gut communities. Here, we describe the identification of type I toxin-antitoxin (TA) systems with the first functional antisense RNAs in this pathogen...
February 26, 2018: Nucleic Acids Research
Alvaro Orell, Vanessa Tripp, Victor Aliaga-Tobar, Sonja-Verena Albers, Vinicius Maracaja-Coutinho, Lennart Randau
Non-coding RNAs (ncRNA) are involved in essential biological processes in all three domains of life. The regulatory potential of ncRNAs in Archaea is, however, not fully explored. In this study, RNA-seq analyses identified a set of 29 ncRNA transcripts in the hyperthermophilic archaeon Sulfolobus acidocaldarius that were differentially expressed in response to biofilm formation. The most abundant ncRNA of this set was found to be resistant to RNase R treatment (RNase R resistant RNA, RrrR(+)) due to duplex formation with a reverse complementary RNA (RrrR(-))...
February 26, 2018: Nucleic Acids Research
Jin-Xin Zheng, Zhi-Wei Lin, Chen Chen, Zhong Chen, Fo-Jun Lin, Yang Wu, Si-Yu Yang, Xiang Sun, Wei-Ming Yao, Duo-Yun Li, Zhi-Jian Yu, Jia-Lin Jin, Di Qu, Qi-Wen Deng
Klebsiella pneumoniae bacteremia biofilm traits and distribution characteristics have not been clarified. This study aimed to determine the prevalence and characteristics of K. pneumoniae bacteremia biofilm formation (BF) and to explore the virulence factors associated with K. pneumoniae BF. A total of 250 K. pneumoniae bacteremia isolates were collected from patients in Shenzhen and Shanghai, China. Virulence genes in their genomes were detected by PCR. The isolates were subjected to multilocus sequence typing (MLST) and clonal complex (CC) classification based on housekeeping genes...
2018: Frontiers in Cellular and Infection Microbiology
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