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MaTAR25: a long non-coding rna involved in breast cancer progression

MOLECULAR & CELLULAR ONCOLOGY 2021年第2期8卷 1882286页

作者： Chang, Kung-Chi Spector, David L. Cold Spring Harbor Lab POB 100 Cold Spring Harbor NY 11724 USA SUNY Stony Brook Mol & Cellular Biol Program Stony Brook NY 11794 USA

We recently reported on the role of Mammary Tumor Associated rna 25 (MaTAR25) in mammary tumor cell proliferation, migration, and invasion. MaTAR25 interacts with transcriptional activator protein Pur-beta (Purb) to regulate its downstream targets such as Tensin1 in trans. The human ortholog of MaTAR25, LINC01271, is upregulated with human breast cancer stage and metastasis.

关键词： lncrna breast cancer non-coding rna tensin 1

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Abstract 1148 GRAS1 non-coding rna protects against DNA damage and cell death

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Journal of Biological Chemistry 2024年第3期300卷 106520-106520页

作者： Wei-Han Chou Tong Su Jonathan Zhu Nhu Trang Colleen McHugh University of California-San Diego

non-coding rna (ncrna) gene products are involved in diverse biological processes including splicing, epigenetic regulation, gene expression, proliferation, and metabolism. The biological mechanisms by which ncrnas may act to regulate cell survival remain poorly understood. We found that a non-coding rna transcript, the Growth Regulator Antisense 1 rna (GRAS1), is a positive regulator of cell growth. Expression of GRAS1 protects lung, colon, and neuronal cells from DNA damage, and loss of GRAS1 triggers cell death. Decreased levels of GRAS1 long non-coding rna (lncrna) resulted in upregulated expression of genes associated with DNA damage response, cell cycle progression, and p53 signaling pathways. Extensive DNA damage occurred within 24 hours of GRAS1 knockdown, with a significant increase in the number of γH2AX foci, indicating multiple double strand breaks per cell. We investigated the function of the GRAS1 gene further since this locus includes four different rna isoforms. We tested the effects of GRAS1 perturbation on cell growth by cloning isoforms of the GRAS1 gene and evaluating the effects of their expression in complementing cell death and DNA damage in GRAS1 knockdown cells.

关键词： non-coding rna DNA damage cell death growth regulation

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Long non-coding rna PTPRG-AS1 promotes cell tumorigenicity in epithelial ovarian cancer by decoying microrna-545-3p and consequently enhancing HDAC4 expression

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Journal of ovarian research 2020年第1期13卷 127页

作者： Juanjuan Shi Xijian Xu Dan Zhang Jiuyan Zhang Hui Yang Chang Li Rui Li Xuan Wei Wenqing Luan Peishu Liu Department of Gynaecology Qilu Hospital Cheeloo College of Medicine Shandong University 107 West Wenhua Road Jinan 277599 Shandong China. Department of Gynaecology Tengzhou Center People's Hospital Zaozhuang 277500 Shandong China. Department of Gynaecology Rizhao Central Hospital Rizhao 276800 Shandong China. Department of TCM Pharmacy Tengzhou Center People's Hospital Zaozhuang 277500 Shandong China. Department of Clinical Pharmacy Tengzhou Center People's Hospital Zaozhuang 277500 Shandong China. Department of Pathology Tengzhou Center People's Hospital Zaozhuang 277500 Shandong China. Department of Gynaecology Qilu Hospital Cheeloo College of Medicine Shandong University 107 West Wenhua Road Jinan 277599 Shandong China. qilu_peishuliu@***.

BACKGROUND:Long non-coding rna PTPRG antisense rna 1 (PTPRG-AS1) deregulation has been reported in various human malignancies and identified as an important modulator of cancer development. Few reports have focused on the detailed role of PTPRG-AS1 in epithelial ovarian cancer (EOC) and its underlying mechanism. This study aimed to determine the physiological function of PTPRG-AS1 in EOC. A series of experiments were also performed to identify the mechanisms through which PTPRG-AS1 exerts its function in EOC. METHODS:Reverse transcription-quantitative polymerase chain reaction was used to determine PTPRG-AS1 expression in EOC tissues and cell lines. PTPRG-AS1 was silenced in EOC cells and studied with respect to cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. The putative mirnas that target PTPRG-AS1 were predicted using bioinformatics analysis and further confirmed in luciferase reporter and rna immunoprecipitation assays. RESULTS:Our data verified the upregulation of PTPRG-AS1 in EOC tissues and cell lines. High PTPRG-AS1 expression was associated with shorter overall survival in patients with EOC. Functionally, EOC cell proliferation, migration, invasion in vitro, and tumor growth in vivo were suppressed by PTPRG-AS1 silencing. In contrast, cell apoptosis was promoted by loss of PTPRG-AS1. Regarding the mechanism, PTPRG-AS1 could serve as a competing endogenous rna in EOC cells by decoying microrna-545-3p (miR-545-3p), thereby elevating histone deacetylase 4 (HDAC4) expression. Furthermore, rescue experiments revealed that PTPRG-AS1 knockdown-mediated effects on EOC cells were, in part, counteracted by the inhibition of miR-545-3p or restoration of HDAC4. CONCLUSIONS:PTPRG-AS1 functioned as an oncogenic lncrna that aggravated the malignancy of EOC through the miR-545-3p/HDAC4 cerna network. Thus, targeting the PTPRG-AS1/miR-545-3p/HDAC4 pathway may be a novel strategy for EOC anticancer therapy.

关键词： Anticancer treatments non-coding rna PTPRG antisense rna 1 cerna

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non-coding rnas at the Eukaryotic rDNA Locus: rna-DNA Hybrids and Beyond

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JOUrnaL OF MOLECULAR BIOLOGY 2020年第15期432卷 4287-4304页

作者： Vydzhak, Olga Luke, Brian Schindler, Natalie Johannes Gutenberg Univ Mainz IMB Ackermannweg 4 D-55128 Mainz Germany Johannes Gutenberg Univ Mainz Inst Dev Biol & Neurobiol IDN D-55128 Mainz Germany

The human ribosomal DNA (rDNA) locus encodes a variety of long non-coding rnas (lncrnas). Among them, the canonical ribosomal rnas that are the catalytic components of the ribosomes, as well as regulatory lncrnas including promoter-associated rnas (prna), stress-induced promoter and pre-rrna antisense rnas (PAPAS), and different intergenic spacer derived lncrna species (IGSrna). In addition, externally encoded lncrnas are imported into the nucleolus, which orchestrate the complex regulation of the nucleolar state in normal and stress conditions via a plethora of molecular mechanisms. This review focuses on the triplex and R-loop formation aspects of lncrnas at the rDNA locus in yeast and human cells. We discuss the protein players that regulate R-loops at rDNA and how their misregulation contributes to DNA damage and disease. Furthermore, we speculate how DNA lesions such as rNMPs or 8-oxo-dG might affect rna-DNA hybrid formation. The transcription of lncrna from rDNA has been observed in yeast, plants, flies, worms, mouse and human cells. This evolutionary conservation highlights the importance of lncrnas in rDNA function and maintenance. (C) 2020 The Authors. Published by Elsevier Ltd.

关键词： rDNA locus non-coding rna rna-DNA hybrid R-loop rna-DNA triplex

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A genomic-library based discovery of a novel, possibly synthetic, acid-tolerance mechanism in Clostridium acetobutylicum involving non-coding rnas and ribosomal rna processing

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METABOLIC ENGINEERING 2010年第3期12卷 268-281页

作者： Borden, Jacob R. Jones, Shawn W. Indurthi, Dinesh Chen, Yili Papoutsakis, Eleftherios Terry Univ Delaware Delaware Biotechnol Inst Newark DE 19711 USA Univ Delaware Dept Chem Engn Newark DE 19711 USA Northwestern Univ Dept Chem & Biol Engn Evanston IL 60208 USA

We generated a genomic library from sheared Clostridium acetobutylicum ATCC 824 DNA, whereby inserts can be expressed in both directions from the thiolase promoter, P-thl. Serial transfer of library-bearing C. acetobutylicum cultures exposed to increasing butyrate concentrations enriched for inserts containing fragments of rrna genetic loci. The selected library inserts were placed so that antisense (to the rrnas) non-coding rnas (ncrnas) would be transcribed from P-thl. Different enriched inserts imparted similar butyrate-tolerance characteristics. A minimal tolerance fragment (RDNA7) was identified as the 16S-rrna promoter region. Expressed on plasmid pRD7 off P-thl, RDNA7 can produce putativen crnas termed ncrna(RD7). C. acetobutylicum 824(pRD7) showed superior resistance to butyrate and other carboxylic acids. Transcriptional analysis of butyrate stress identified 120 differentially expressed genes between 824(pRD7) and 824(pSOS95del). The few upregulated genes included the ffh gene of the putative signal recognition particle (SRP) system. Northern analysis of nc rna(RD7) and corresponding antisense rnas demonstrated multiple ncrna(RD7) molecules in 824(pRD7). Several corresponding antisense rna molecules were identified both in 824(pRD7) and 824 (pSOS95del), but at much higher levels in 824(pRD7). Northern analysis of 16S rrna expression suggested complex RDNA7-dependent rrna processing. Our data suggest that by hybridizing against unprocessed rrna precursors, ncrna(RD7) alters rrna processing, and these alterations result in acid tolerance, possibly through a mechanism involving the Ffh protein. (C) 2010 Elsevier Inc. All rights reserved.

关键词： Genomic library rrna processing non-coding rna Acid tolerance Synthetic phenotype ffh Signal recognition particle Sense and antisense libraries

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rna sequencing of transcriptomes in human brain regions: protein-coding and non-coding rnas, isoforms and alleles

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BMC GENOMICS 2015年第1期16卷 1-16页

作者： Webb, Amy Papp, Audrey C. Curtis, Amanda Newman, Leslie C. Pietrzak, Maciej Seweryn, Michal Handelman, Samuel K. Rempala, Grzegorz A. Wang, Daqing Graziosa, Erica Tyndale, Rachel F. Lerman, Caryn Kelsoe, John R. Mash, Deborah C. Sadee, Wolfgang Ohio State Univ Coll Med Ctr Pharmacogen Columbus OH 43210 USA Ohio State Univ Dept Biomed Informat Coll Med Columbus OH 43210 USA Ohio State Univ Coll Publ Hlth Div Biostat Columbus OH 43210 USA Ohio State Univ Math Biosci Inst Columbus OH 43210 USA Thermo Fisher Sci San Francisco CA 94080 USA Univ Toronto Ctr Addict & Mental Hlth Toronto ON Canada Univ Toronto Dept Psychiat Toronto ON Canada Univ Toronto Dept Pharmacol & Toxicol Toronto ON Canada Univ Penn Dept Psychiat Annenberg Sch Commun Philadelphia PA 19104 USA Univ Penn Abramson Canc Ctr Philadelphia PA 19104 USA Univ Calif San Diego Lab Psychiat Genom Dept Psychiat San Diego CA 92103 USA VA San Diego Healthcare Syst San Diego CA USA Univ Miami Miller Sch Med Dept Neurol Miami FL 33136 USA Ohio State Univ Coll Med Dept Pharmacol Columbus OH 43210 USA Ohio State Univ Coll Pharm Dept Pharmacol Columbus OH 43210 USA Ohio State Univ Coll Environm Hlth Dept Pharmacol Columbus OH 43210 USA Ohio State Univ Coll Med Dept Psychiat Columbus OH 43210 USA Ohio State Univ Coll Pharm Dept Psychiat Columbus OH 43210 USA Ohio State Univ Coll Environm Hlth Sci Dept Psychiat Columbus OH 43210 USA Ohio State Univ Coll Med Dept Human Genet Columbus OH 43210 USA Ohio State Univ Coll Med Dept Internal Med Columbus OH 43210 USA Ohio State Univ Coll Pharm Columbus OH 43210 USA Ohio State Univ Coll Environm Hlth Sci Columbus OH 43210 USA

Background: We used rna sequencing to analyze transcript profiles of ten autopsy brain regions from ten subjects. rna sequencing techniques were designed to detect both coding and non-coding rna, splice isoform composition, and allelic expression. Brain regions were selected from five subjects with a documented history of smoking and five non-smokers. Paired-end rna sequencing was performed on SOLiD instruments to a depth of >40 million reads, using linearly amplified, ribosomally depleted rna. Sequencing libraries were prepared with both poly-dT and random hexamer primers to detect all rna classes, including long non-coding (lncrna), intronic and intergenic transcripts, and transcripts lacking poly-A tails, providing additional data not previously available. The study was designed to generate a database of the complete transcriptomes in brain region for gene network analyses and discovery of regulatory variants. Results: Of 20,318 protein coding and 18,080 lncrna genes annotated from GENCODE and lncipedia, 12 thousand protein coding and 2 thousand lncrna transcripts were detectable at a conservative threshold. Of the aligned reads, 52 % were exonic, 34 % intronic and 14 % intergenic. A majority of protein coding genes (65 %) was expressed in all regions, whereas ncrnas displayed a more restricted distribution. Profiles of rna isoforms varied across brain regions and subjects at multiple gene loci, with neurexin 3 (NRXN3) a prominent example. Allelic rna ratios deviating from unity were identified in >400 genes, detectable in both protein-coding and non-coding genes, indicating the presence of cis-acting regulatory variants. Mathematical modeling was used to identify rnas stably expressed in all brain regions (serving as potential markers for normalizing expression levels), linked to basic cellular functions. An initial analysis of differential expression analysis between smokers and nonsmokers implicated a number of genes, several previously associated with nicotin

关键词： rna sequencing Brain regions Differential expression Allelic expression imbalance Isoform fraction non-coding rna

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Analysis of long non-coding rnas produced by a specialized rna polymerase in Arabidopsis thaliana

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METHODS 2013年第2期63卷 160-169页

作者： Rowley, M. Jordan Boehmdorfer, Gudrun Wierzbicki, Andrzej T. Univ Michigan Dept Mol Cellular & Dev Biol Ann Arbor MI 48109 USA

Long non-coding rnas (Incrnas) play important roles in several processes including control of gene expression. In Arabidopsis thaliana, a class of Incrnas is produced by a specialized rna Polymerase V (Pol V), which is involved in controlling genome activity by transcriptional gene silencing. Incrnas produced by Pol V have been proposed to serve as scaffolds for binding of several silencing factors which further mediate the establishment of repressive chromatin modifications. We present methods for discovery and characterization of Incrnas produced by Pol V. Chromatin Immunoprecipitation coupled with deep sequencing (ChIP-seq) allows discovery of genomic regions bound by proteins in a manner dependent on either Pol V or transcripts produced by Pol V. rna Immunoprecipitation (RIP) allows testing Incrna-protein interactions at identified loci. Finally, real-time RT-PCR allows detection of low abundance Pol V transcripts from total rna. These methods may be more broadly applied to discovery and characterization of rnas produced by distinct rna Polymerases. (C) 2013 Elsevier Inc. All rights reserved.

关键词： non-coding rna ChIP Gene silencing rna Polymerase RIP

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ncrnaseq: simple modifications to rna-seq library preparation allow recovery and analysis of mid-sized non-coding rnas

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BIOTECHNIQUES 2021年第1期72卷 21-28页

作者： Minshall, Nicola Chernukhin, Igor Carroll, Jason S. Git, Anna Univ Cambridge Canc Res UK Cambridge Inst Cambridge England Univ Cambridge Dept Biochem Cambridge England

Despite their abundance, mid-sized rnas (30-300 nt) have not been extensively studied by high-throughput sequencing, mostly due to selective loss in library preparation. The authors propose simple and inexpensive modifications to the Illumina TruSeq protocol (ncrnaseq), allowing the capture and sequencing of mid-sized non-coding rnas without detriment to the coverage of coding mrnas. This protocol is coupled with a two-step alignment: a pre-alignment to a curated non-coding genome, passing only the non-mapping reads to a standard genomic alignment. ncrnaseq correctly assigns the highest read-numbers to established abundant non-coding rnas and correctly identifies cytosolic and nuclear enrichment of known non-coding rnas in two cell lines. METHOD SUMMARY In order to retain rnas shorter than 300 nt and the cDNAs they give rise to, the authors reduce the fractionation time of the rna and increase the efficiency of four precipitation steps in the Illumina TruSeq protocol (ncrnaseq): twice pre-ligation by adding isopropanol to AMPure beads and twice post-ligation by using a higher AMPure-to-sample ratio. The resulting sequencing reads are aligned first to a custom non-redundant curated 'non-coding genome', which allows the user to exert control, for example, on amalgamation of multi-copy genes or separation of non-coding intronic gene counts from coding host gene counts. The non-mapping reads are then passed to a standard genomic alignment in a lossless manner.

关键词： 5 ' coverage high-throughput sequencing next-generation sequencing non-coding rna size-selection

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non-coding rnas to treat vascular smooth muscle cell dysfunction

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BRITISH JOUrnaL OF PHARMACOLOGY 2025年第2期182卷 246-280页

作者： Brown, Simon D. Klimi, Eftychia Bakker, Wilfried A. M. Beqqali, Abdelaziz Baker, Andrew H. Univ Edinburgh Queens Med Res Inst BHF Ctr Cardiovasc Sci 47 Little France Crescent Edinburgh EH16 4TJ Scotland Btavia Biosci BV Biosci Pk Leiden Leiden Netherlands Maastricht Univ Med Ctr Cardiovasc Res Inst Maastricht CARIM Maastricht Netherlands

Vascular smooth muscle cell (vSMC) dysfunction is a critical contributor to cardiovascular diseases, including atherosclerosis, restenosis and vein graft failure. Recent advances have unveiled a fascinating range of non-coding rnas (ncrnas) that play a pivotal role in regulating vSMC function. This review aims to provide an in-depth analysis of the mechanisms underlying vSMC dysfunction and the therapeutic potential of various ncrnas in mitigating this dysfunction, either preventing or reversing it. We explore the intricate interplay of micrornas, long-non-coding rnas and circular rnas, shedding light on their roles in regulating key signalling pathways associated with vSMC dysfunction. We also discuss the prospects and challenges associated with developing ncrna-based therapies for this prevalent type of cardiovascular pathology. image

关键词： atherosclerosis cardiovascular disease circular rna long non-coding rna microrna non-coding rna therapeutic oligonucleotides vascular smooth muscle cell

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non-coding rnas, a double-edged sword in breast cancer prognosis

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CANCER CELL INTErnaTIONAL 2025年第1期25卷 1-31页

作者： Solaimani, Maryam Hosseinzadeh, Sahar Abasi, Mozhgan Amol Univ Special Modern Technol Fac Biotechnol Amol Iran Mazandaran Univ Med Sci Fac Pharm & Med Biotechnol Sari Iran Mazandaran Univ Med Sci Fac Adv Technol Med Immunogenet Res Ctr Dept Tissue Engn & Appl Cell Sci POB 48175-861 Sari Iran

Cancer is a rising issue worldwide, and numerous studies have focused on understanding the underlying reasons for its occurrence and finding proper ways to defeat it. By applying technological advances, researchers are continuously uncovering and updating treatments in cancer therapy. Their vast functions in the regulation of cell growth and proliferation and their significant role in the progression of diseases, including cancer. This review provides a comprehensive analysis of ncrnas in breast cancer, focusing on long non-coding rnas such as HOTAIR, MALAT1, and NEAT1, as well as micrornas such as miR-21, miR-221/222, and miR-155. These ncrnas are pivotal in regulating cell proliferation, metastasis, drug resistance, and apoptosis. Additionally, we discuss experimental approaches that are useful for studying them and highlight the advantages and challenges of each method. We then explain the results of these clinical trials and offer insights for future studies by discussing major existing gaps. On the basis of an extensive number of studies, this review provides valuable insights into the potential of ncrnas in cancer therapy. Key findings show that even though the functions of ncrnas are vast and undeniable in cancer, there are still complications associated with their therapeutic use. Moreover, there is an absence of sufficient experiments regarding their application in mouse models, which is an area to work on. By emphasizing the crucial role of ncrnas, this review underscores the need for innovative approaches and further studies to explore their potential in cancer therapy.

关键词： Breast cancer-carcinoma Neoplasia non-coding rna Long non-coding rna Oncogene Tumor suppressor

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