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Repression of transposable-elements - a microrna anti-cancer defense mechanism?

TRENDS IN GENETICS 2010年第6期26卷 253-259页

作者： Shalgi, Reut Pilpel, Yitzhak Oren, Moshe Weizmann Inst Sci Dept Mol Genet IL-76100 Rehovot Israel Weizmann Inst Sci Dept Mol Cell Biol IL-76100 Rehovot Israel

Micrornas (mirnas) appear to be key players in the maintenance of genomic integrity. Recent evidence implies that cancers often avoid mirna-mediated regulation, and global repression of mirnas is associated with increased tumorigenicity. Here we suggest that mirnas are directly involved in the maintenance of genomic integrity through global repression of transposable elements (TEs), whose expression and transposition are well-documented causes of genomic instability in mammalian somatic tissues. Hence, one outcome of the tumor's ability to avoid mirna-mediated regulation might be the enhancement of genomic instability and mutability due to derepression of TEs. We outline possible mechanisms underlying TE repression by mirnas, including post-transcriptional silencing and transcriptional silencing through DNA and histone methylation. This hypothesis calls into consideration the need to study the role of mirnas and the rnai machinery in the nucleus, and specifically their impact on the maintenance of genomic integrity in the context of cancer.

关键词： GENETIC regulation TRANSPOSONS non-coding rna GENETIC repressors MOLECULAR genetics ANTINEOPLASTIC agents TRANSLOCATION (Genetics) GENE silencing MUTATION (Biology)

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New challenges in hepatocellular carcinoma:A role for PIWIinteracting rnas?

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World Journal of Gastroenterology 2024年第22期30卷 2843-2848页

作者： Domenico Tierno Gabriele Grassi Bruna Scaggiante Department of Medicine Surgery and Health SciencesUniversity Hospital of CattinaraUniversity of TriesteTrieste 34149Italy Department of Life Sciences University of TriesteTrieste 34127Italy

Hepatocellular carcinoma(HCC)is the most common and deadliest subtype of liver cancer worldwide and,therefore,poses an enormous threat to global *** the molecular mechanisms underlying the development and progression of HCC is central to improving our clinical *** rnas(pirnas)are a class of small non-coding rnas that bind to PIWI family proteins to regulate gene expression at transcriptional and posttranscriptional levels.A growing body of work shows that the dysregulation of pirnas plays a crucial role in the progression of various human *** this editorial,we report on the current knowledge of HCC-associated pirnas and their potential clinical *** on the editorial by Papadopoulos and Trifylli,on the role and clinical evaluation of exosomal circular rnas in HCC,we highlight this other emerging class of non-coding rnas.

关键词： Biomarker Hepatocellular carcinoma Liquid biopsy non-coding rna PIWI-interacting rna Next-generation sequencing

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Transcript catalogs of human chromosome 21 and orthologous chimpanzee and mouse regions

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MAMMALIAN GENOME 2011年第5-6期22卷 261-271页

作者： Sturgeon, Xiaolu Gardiner, Katheleen J. Univ Colorado Denver Intellectual & Dev Disabil Res Ctr Neurosci & Human Med Genet Programs Aurora CO 80045 USA Univ Colorado Denver Dept Pediat Computat Biosci Program Aurora CO 80045 USA

A comprehensive representation of the gene content of the long arm of human chromosome 21 (Hsa21q) remains of interest for the study of Down syndrome, its associated phenotypic features, and mouse models. Here we compare transcript catalogs for Hsa21q, chimpanzee chromosome 21 (Ptr21q), and orthologous regions of mouse chromosomes 16, 17, and 10 for open reading frame (ORF) characteristics and conservation. The Hsa21q and mouse catalogs contain 552 and 444 gene models, respectively, of which only 162 are highly conserved. Hsa21q transcripts were used to identify orthologous exons in Ptr21q and assemble 533 putative transcripts. Transcript catalogs for all three organisms are searchable for nucleotide and amino acid sequence features of ORF length, repeat content, experimental support, gene structure, and conservation. For human and mouse comparisons, three additional summaries are provided: (1) the chromosomal distribution of novel ORF transcripts versus potential functional rnas, (2) the distribution of species-specific transcripts within Hsa21q and mouse models of Down syndrome, and (3) the organization of sense-antisense and putative sense-antisense structures defining potential regulatory mechanisms. Catalogs, summaries, and nucleotide and amino acid sequences of all composite transcripts are available and searchable at http://***/iddrc/chr21/***. These data sets provide comprehensive information useful for evaluation of candidate genes and mouse models of Down syndrome and for identification of potential functional rna genes and novel regulatory mechanisms involving Hsa21q genes. These catalogs and search tools complement and extend information available from other gene annotation projects.

关键词： HUMAN chromosome 21 GENETIC transcription DOWN syndrome MICE as laboratory animals CHIMPANZEES as laboratory animals non-coding rna GENETIC aspects

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Molecular predictors of metastasis in patients with prostate cancer

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EXPERT REVIEW OF MOLECULAR DIAGNOSTICS 2023年第3期23卷 199-215页

作者： Lin, Jundong Zhuo, Yangjia Zhang, Yixun Liu, Ren Zhong, Weide South China Univ Technol Affiliated Hosp 2 Sch Med Dept Urol Guangzhou Guangdong Peoples R China South China Univ Technol Guangzhou Peoples Hosp 1 Sch Med Guangdong Key Lab Clin Mol Med & Diagnost Guangzhou Guangdong Peoples R China South China Univ Technol Affiliated Hosp 2 Sch Med Dept Urol Guangzhou 510180 Guangdong Peoples R China

IntroductionProstate cancer is a serious threat to the health of older adults worldwide. The quality of life and survival time of patients sharply decline once metastasis occurs. Thus, early screening for prostate cancer is very advanced in developed countries. The detection methods used include Prostate-specific antigen (PSA) detection and digital rectal examination. However, the lack of universal access to early screening in some developing countries has resulted in an increased number of patients presenting with metastatic prostate cancer. In addition, the treatment methods for metastatic and localized prostate cancer are considerably different. In many patients, early-stage prostate cancer cells often metastasize due to delayed observation, negative PSA results, and delay in treatment time. Therefore, the identification of patients who are prone to metastasis is important for future clinical *** coveredthis review introduced a large number of predictive molecules related to prostate cancer metastasis. These molecules involve the mutation and regulation of tumor cell genes, changes in the tumor microenvironment, and the liquid *** opinionIn next decade, PSMA PET/CT and liquid biopsy will be the excellent predicting tools, while (177) Lu- PSMA-RLT will be showed excellent anti-tumor efficacy in mPCa patients.

关键词： Bodily fluids gene expression gene mutation metastatic prostate cancer non-coding rna predictors tumor microenvironment

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Microrna-93 regulates NRF2 expression and is associated with breast carcinogenesis

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CARCINOGENESIS 2013年第5期34卷 1165-1172页

作者： Singh, Bhupendra Ronghe, Amruta M. Chatterjee, Anwesha Bhat, Nimee K. Bhat, Hari K. Univ Missouri Sch Pharm Div Pharmacol & Toxicol Kansas City MO 64108 USA

Micrornas (mirna) are small non-coding rnas that regulate the expression of approximately 60% of all human genes and play important roles in disease processes. Recent studies have demonstrated a link between dysregulated expression of mirnas and breast carcinogenesis. Long-term estrogen exposure is implicated in development of human breast cancers, yet underlying mechanisms remain elusive. We have recently demonstrated that antioxidant vitamin C (vit C) prevents estrogen-induced breast tumor development. In this study, we investigated the role of vit C in the regulation of microrna-93 (miR-93) and its target gene(s) in a rat model of mammary carcinogenesis. Female August Copenhagen Irish (ACI) rats were treated with vit C in the presence or absence of 17-estradiol (E2) for 8 months. We demonstrate an increased expression of the miR-93 in E2-treated mammary tissues and in human breast cell lines and vit C treatment reverted E2-mediated increase in miR-93 levels. Mirna target prediction programs suggest one of the target genes of miR-93 to be nuclear factor erythroid 2-related factor 2 (NRF2). In contrast with miR-93 expression, NRF2 protein expression was significantly decreased in E2-treated mammary tissues, mammary tumors, and in breast cancer cell lines, and its expression was significantly increased after vit C treatment. Ectopic expression of miR-93 decreased protein expression of NRF2 and NRF2-regulated genes. Furthermore, miR-93 decreased apoptosis, increased colony formation, mammosphere formation, cell migration and DNA damage in breast epithelial cells, whereas silencing of miR-93 in these cells inhibited these carcinogenic processes. Taken together, our findings suggest an oncogenic potential of miR-93 during E2-induced breast carcinogenesis.

关键词： MICROrna GENETIC regulation NF-kappa B (DNA-binding protein) BREAST cancer -- Genetic aspects GENE expression CARCINOGENESIS non-coding rna

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Themes and variations in riboswitch structure and function

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BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS 2014年第10期1839卷 908-918页

作者： Peselis, Alla Serganov, Alexander NYU Sch Med Dept Biochem & Mol Pharmacol New York NY 10016 USA

The complexity of gene expression control by non-coding rna has been highlighted by the recent progress in the field of riboswitches. Discovered a decade ago, riboswitches represent a diverse group of non-coding mrna regions that possess a unique ability to directly sense cellular metabolites and modulate gene expression through formation of alternative metabolite-free and metabolite-bound conformations. Such protein-free metabolite sensing domains utilize sophisticated three-dimensional folding of rna molecules to discriminate between a cognate ligand from related compounds so that only the right ligand would trigger a genetic response. Given the variety of riboswitch ligands ranging from small cations to large coenzymes, riboswitches adopt a great diversity of structures. Although many riboswitches share structural principles to build metabolite-competent folds, form precise ligand-binding pockets, and communicate a ligand-binding event to downstream regulatory regions, virtually all riboswitch classes possess unique features for ligand recognition, even those tuned to recognize the same metabolites. Here we present an overview of the biochemical and structural research on riboswitches with a major focus on common principles and individual characteristics adopted by these regulatory rna elements during evolution to specifically target small molecules and exert genetic responses. This article is part of a Special Issue entitled: Riboswitches. (c) 2014 Elsevier B.V. All rights reserved.

关键词： rna structure X-ray crystallography Metabolite Gene expression Transcription non-coding rna

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The emerging role of rna in the regulation of gene transcription in human cells

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SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY 2011年第4期22卷 351-358页

作者： Morris, Kevin V. Scripps Res Inst Dept Mol & Expt Med La Jolla CA 92037 USA

Recent evidence suggests that particular species of non-coding rnas can modulate gene transcription in human cells. While such observations were in the past relegated to imprinted genes, it is now becoming apparent that several different genes in differentiated cells may be under some form of rna based regulatory control. Studies carried out to date have begun to discern the mechanism of action whereby non-coding rnas modulate gene transcription by the targeted recruitment of epigenetic silencing complexes to homology containing loci in the genome. The results of these studies will be considered in detail as well as the implications that a vast array of non-coding rna based regulatory networks may be operative in human cells. (C) 2011 Elsevier Ltd. All rights reserved.

关键词： Concordant Discordant Transcriptional silencing non-coding rna Epigenetic

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Circ-ZNF609 Is a Circular rna that Can Be Translated and Functions in Myogenesis

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MOLECULAR CELL 2017年第1期66卷 22-+页

作者： Legnini, Ivano Di Timoteo, Gaia Rossi, Francesca Morlando, Mariangela Briganti, Francesca Sthandier, Olga Fatica, Alessandro Santini, Tiziana Andronache, Adrian Wade, Mark Laneve, Pietro Rajewsky, Nikolaus Bozzoni, Irene Sapienza Univ Rome Dept Biol & Biotechnol Charles Darwin P Moro 5 I-00185 Rome Italy Sapienza Univ Rome IBPM P Moro 5 I-00185 Rome Italy Ist Italiano Tecnol Ctr Life Nano Sci Sapienza Viale Regina Elena 291 I-00161 Rome Italy Fdn Ist Italiano Tecnol IIT Ctr Genom Sci IIT SEMM Via Adamello 16 I-20139 Milan Italy Max Delbruck Ctr Mol Med Berlin Inst Med Syst Biol Robert Rossle Str 10 D-13125 Berlin Germany Sapienza Univ Rome Fdn Cenci Bolognetti Inst Pasteur Italy P Moro 5 I-00185 Rome Italy

Circular rnas (circrnas) constitute a family of transcripts with unique structures and still largely unknown functions. Their biogenesis, which proceeds via a back-splicing reaction, is fairly well characterized, whereas their role in the modulation of physiologically relevant processes is still unclear. Here we performed expression profiling of circrnas during in vitro differentiation of murine and human myoblasts, and we identified conserved species regulated in myogenesis and altered in Duchenne muscular dystrophy. A high-content functional genomic screen allowed the study of their functional role in muscle differentiation. One of them, circ-ZNF609, resulted in specifically controlling myoblast proliferation. Circ-ZNF609 contains an open reading frame spanning from the start codon, in common with the linear transcript, and terminating at an in-frame STOP codon, created upon circularization. Circ-ZNF609 is associated with heavy polysomes, and it is translated into a protein in a splicing-dependent and cap-independent manner, providing an example of a protein-coding circrna in eukaryotes.

关键词： circrna circular rna myogenesis muscle differentiation translation cap independent DMD proliferation non-coding rna

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Small nucleolar rna genes

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RUSSIAN JOUrnaL OF GENETICS 2007年第2期43卷 97-105页

作者： Makarova, J. A. Kramerov, D. A. Russian Acad Sci Engelhardt Inst Mol Biol Moscow 119991 Russia

Small nucleolar rnas (snornas) are one of the most numerous and well-studied groups of nonprotein-coding rnas. In complex with proteins, snornas perform the two most common nucleotide modifications in rrna: 2'-OH-methylation of ribose and pseudouridylation. Although the modification mechanisms and snoRNP structures are highly conserved, the snorna genes are surprisingly diverse in organization. In addition to genes transcribed independently, there are genes that are in introns of other genes, form clusters transcribed from a common promoter, or clusters in introns. Interestingly, one type of gene organization usually prevails in different taxa. Vertebrate snornas mostly originate from introns of protein-coding genes;a small group of snornas are encoded by introns of genes for noncoding rnas.

关键词： rna non-coding rna HEREDITY GENES INTRONS SPLIT genes NUCLEIC acids TRANSCRIPTION DOUBLE-stranded rna

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Cycling of the Sm-like protein Hfq on the DsrA small regulatory rna

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JOUrnaL OF MOLECULAR BIOLOGY 2004年第5期344卷 1211-1223页

作者： Lease, RA Woodson, SA Johns Hopkins Univ TC Jenkins Dept Biophys Baltimore MD 21218 USA

Small rnas (srnas) regulate bacterial genes involved in environmental adaptation. This rna regulation requires Hfq, a bacterial Sm-like protein that stabilizes srnas and enhances rna-rna interactions. To understand the mechanism of target recognition by srnas, we investigated the interactions between Hfq, the srna DsrA, and its regulatory target rpoS mrna, which encodes the stress response sigma factor. Nuclease footprinting revealed that Hfq recognized multiple sites in rpoS mrna without significantly perturbing secondary structure in the 5' leader that inhibits translation initiation. Base-pairing with DsrA, however, made the rpoS ribosome binding site fully accessible, as predicted by genetic data. Hfq bound DsrA four times more tightly than the DsrA (.) rpoS rna complex in gel mobility-shift assays. Consequently, Hfq is displaced rapidly from its high-affinity binding site on DsrA by conformational changes in DsrA, when DsrA base-pairs with rpoS mrna. Hfq accelerated DsrA (.) rpoS rna association and stabilized the rna complex up to twofold. Hybridization of DsrA and rpoS mrna was optimal when Hfq occupied its primary binding site on free DsrA, but was inhibited when Hfq associated with the DsrA (.) rpoS rna complex. We conclude that recognition of rpoS mrna is stimulated by binding of Hfq to free DsrA srna, followed by release of Hfq from the srna (.) mrna complex. (C) 2004 Elsevier Ltd. All rights reserved.

关键词： anti-sense rna rna chaperone non-coding rna rna-protein interactions riboregulation

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