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Circ-104916 is downregulated in gastric cancer and suppresses migration and invasion of gastric cancer cells

ONCOTARGETS AND THERAPY 2017年 10卷 3521-3529页

作者： Li, Jin Zhen, Li Zhang, Yan Zhao, Liying Liu, Hao Cai, Danxian Chen, Hao Yu, Jiang Qi, Xiaolong Li, Guoxin Southern Med Univ Nanfang Hosp Dept Gen Surg 1838 North Guangzhou Ave Guangzhou 510515 Guangdong Peoples R China

Circular rnas are a large class of noncoding rna that have shown huge capabilities as gene regulators. Recent evidence suggest that circular rnas are associated with many diseases, especially cancer. However, little attention has been focused on the expression and function of circular rna in gastric cancer (GC). In this study, we demonstrate that the expression of circ-104916 is downregulated in GC tissues and cell lines. A lower expression of circ-104916 appeared in deeper invasion depth, higher tumor stage and more frequent lymphatic metastasis patients. Overexpression of circ-104916 effectively inhibited the proliferation, migration and invasion abilities of GC cells in vitro. Western blot showed that circ-104916 overexpression upregulated E-cadherin and downregulated N-cadherin, Vimentin and Slug, indicating that circ-104916 was involved in the epithelial-mesenchymal transition process. Our results revealed that circ-104916 might be a novel potential tumor suppressor and biomarker of GC.

关键词： circular rna noncoding rna circ-104916 gastric cancer EMT

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Alpha satellite DNA biology: finding function in the recesses of the genome

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CHROMOSOME RESEARCH 2018年第3期26卷 115-138页

作者： McNulty, Shannon M. Sullivan, Beth A. Duke Univ Med Ctr Dept Mol Genet & Microbiol Durham NC 27710 USA Duke Univ Med Ctr Div Human Genet Durham NC 27710 USA

Repetitive DNA, formerly referred to by the misnomer junk DNA, comprises a majority of the human genome. One class of this DNA, alpha satellite, comprises up to 10% of the genome. Alpha satellite is enriched at all human centromere regions and is competent for de novo centromere assembly. Because of thehighly repetitive nature ofalpha satellite, ithas been difficult to achieve genome assemblies at centromeres using traditional next-generation sequencing approaches, and thus, centromeres represent gaps in the current human genome assembly. Moreover, alpha satellite DNA is transcribed into repetitive noncoding rna and contributes to a large portion of the transcriptome. Recent efforts to characterize these transcripts and their function have uncovered pivotal roles for satellite rna in genome stability, including silencing selfish DNA elements and recruiting centromere and kinetochore proteins. This review will describe the genomic and epigenetic features of alpha satellite DNA, discuss recent findings of noncoding transcripts produced from distinct alpha satellite arrays, and address current progress in the functional understanding of this oft-neglected repetitive sequence. We will discuss unique challenges of studying human satellite DNAs and rnas and point toward new technologies that will continue to advance our understanding of this largely untapped portion of the genome.

关键词： satellite centromere kinetochore variation transcription noncoding rna repetitive DNA epiallele

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Non-coding rnas in Alzheimer's Disease

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MOLECULAR NEUROBIOLOGY 2013年第1期47卷 382-393页

作者： Tan, Lin Yu, Jin-Tai Hu, Nan Tan, Lan Qingdao Univ Dept Neurol Qingdao Municipal Hosp Sch Med Qingdao 266071 Shandong Peoples R China Ocean Univ China Coll Med & Pharmaceut Qingdao 266003 Peoples R China

Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most common dementia among the elderly. Accumulating research indicates that noncoding rnas (ncrnas), especially micrornas (mirnas) and long noncoding rnas (lncrnas), are increasingly being implicated in AD. Mirnas are conserved small ncrnas that control gene expression post-transcriptionally while lncrnas function in many ways. Recent profiling research in human or mouse models suggests that mirnas are aberrantly expressed in AD, and these have been implicated in the regulation of amyloid-beta (A beta) peptide, tau, inflammation, cell death, and other aspects which are the main pathomechanisms of AD. In addition, regulation of mirnas varies in blood, and cerebral spinal fluid may indicate alterations in AD. Together with brain-specific mirnas, these mirnas could be potential AD biomarkers. All the above may provide the basis for new approaches for AD. Here, we review current findings regarding ncrna research in human and mouse models to provide a strong basis for future study aiming at promising contributions of ncrna in AD.

关键词： noncoding rna Alzheimer's disease microrna Long noncoding rna Small interfering rna

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Making sense of the natural antisense transcript puzzle

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TRENDS IN PLANT SCIENCE 2021年第11期26卷 1104-1115页

作者： Reis, Rodrigo Siqueira Poirier, Yves Univ Lausanne Dept Plant Mol Biol CH-1015 Lausanne Switzerland

In plants, thousands of genes are associated with antisense transcription, which often produces noncoding rnas. Although widespread, sense-antisense pairs have been implicated in a limited variety of functions in plants and are often thought to form extensive dsrna stretches triggering gene silencing. In this opinion, we show that evidence does not support gene silencing as a major role for antisense transcription. In fact, it is more likely that antisense transcripts play diverse functions in gene regulation. We propose a general framework for the initial functional dissection of antisense transcripts, suggesting testable hypotheses relying on an experiment-based decision tree. By moving beyond the gene silencing paradigm, we argue that a broad and diverse role for natural antisense transcription will emerge.

关键词： natural antisense transcript noncoding rna rna–rna interaction silencing

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Early termination of the Shiga toxin transcript generates a regulatory small rna

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2020年第40期117卷 25055-25065页

作者： Sy, Brandon M. Lan, Ruiting Tree, Jai J. Univ New South Wales Sch Biotechnol & Biomol Sci Sydney NSW 2052 Australia

Enterohemorrhagic Escherichia coli is a significant human pathogen that causes disease ranging from hemorrhagic colitis to hemolytic uremic syndrome. The latter can lead to potentially fatal renal failure and is caused by the release of Shiga toxins that are encoded within lambdoid bacteriophages. The toxins are encoded within the late transcript of the phage and are regulated by anti-termination of the P-R' late promoter during lytic induction of the phage. During lysogeny, the late transcript is prematurely terminated at t(R)' immediately downstream of P-R', generating a short rna that is a byproduct of antitermination regulation. We demonstrate that this short transcript binds the small rna chaperone Hfq, and is processed into a stable 74-nt regulatory small rna that we have termed StxS. StxS represses expression of Shiga toxin 1 under lysogenic conditions through direct interactions with the stx1AB transcript. StxS acts in trans to activate expression of the general stress response sigma factor, RpoS, through direct interactions with an activating seed sequence within the 5 ' UTR. Activation of RpoS promotes high cell density growth under nutrient-limiting conditions. Many phages utilize antitermination to regulate the lytic/lysogenic switch and our results demonstrate that short rnas generated as a byproduct of this regulation can acquire regulatory small rna functions that modulate host fitness.

关键词： srna lambda phage Shiga toxin ncrna noncoding rna

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Non-coding rna and cholesteatoma

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LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY 2022年第1期7卷 60-66页

作者： Jovanovic, Ivan Zivkovic, Maja Jesic, Snezana Stankovic, Aleksandra Univ Belgrade VINCA Inst Nucl Sci Natl Inst Republ Serbia Lab Radiobiol & Mol Genet POB 522 Belgrade 11001 Serbia Univ Belgrade Med Fac Belgrade Belgrade Serbia Clin Ctr Serbia Clin Otorhinolaryngol & Maxillofacial Surg Belgrade Serbia

Objective Cholesteatoma is a challenging chronic pathology of the middle ear for which pharmacologic therapies have not been developed yet. Cholesteatoma occurrence depends on the interplay between genetic and environmental factors while master regulators orchestrating disease progression are still unknown. Therefore, in this review, we will discuss the diagnostic and therapeutic potential of non-coding rnas (ncrna) as a new class of regulatory molecules. Methods We have comprehensively reviewed all articles investigating ncrnas, specifically micro rnas (mirnas) and long ncrnas (lncrna/circrna) in cholesteatoma tissue. Results Candidate mirna approaches indicated that miR-21 and let-7a are the major mirnas involved in cholesteatoma growth, migration, proliferation, bone destruction, and apoptosis. Regulatory potential for the same biological processes was also observed for miR-203a. The NF-kB/miR-802/PTEN regulatory network was in relation to observed miR-21 activity in cholesteatoma as well. High throughput approaches revealed additional ncrnas implicated in cholesteatoma pathology. Competitive endogenous rna (cerna) analysis highlighted lncrna/circrna that could be "endogenous sponge" for miR-21 and let-7a based on the hypothesis that rna transcripts can communicate with and regulate each other by using shared mirna response elements. Conclusion In this review, we summarize the discoveries and role of ncrna in major pathways in cholesteatoma and highlight the potential of mirna-based therapeutics in the treatment of cholesteatoma.

关键词： cholesteatoma long noncoding rna micro rna noncoding rna rna interaction

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Drug resistance in colorectal cancer: An epigenetic overview

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BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER 2021年第2期1876卷 188623-188623页

作者： Luo, Maochao Yang, Xingyue Chen, Hai-Ning Nice, Edouard C. Huang, Canhua Ningbo Univ Affiliated Hosp Med Sch Ningbo 315020 Zhejiang Peoples R China Sichuan Univ State Key Lab Biotherapy & Canc Ctr West China HospCollaborat Innovat Ctr Biotherapy West China Sch Basic Med Sci & Forens Med Chengdu 610041 Peoples R China Sichuan Univ State Key Lab Biotherapy & Canc Ctr Dept Gastrointestinal Surg West China Hosp Chengdu 610041 Peoples R China Monash Univ Dept Biochem & Mol Biol Clayton Vic Australia

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Despite significant progress that has been made in therapies against CRC over the past decades, drug resistance is still a major limitation in CRC treatment. Numerous investigations have unequivocally shown that epigenetic regulation plays an important role in CRC drug resistance because of the high rate of epigenetic alterations in multiple genes during cancer development or drug treatment. Furthermore, the reversibility of epigenetic alterations provides novel therapeutic strategies to overcome drug resistance using small molecules, which can target non-coding rnas or reverse histone modification and DNA methylation. In this review, we discuss epigenetic regulation in CRC drug resistance and the possible role of preventing or reversing CRC drug resistance using epigenetic therapy in CRC treatment.

关键词： Colorectal cancer Drug resistance DNA methylation Histone modification noncoding rna

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Involvement of mirnas and Cell-Secreted Vesicles in Mammalian Ovarian Antral Follicle Development

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REPRODUCTIVE SCIENCES 2015年第12期22卷 1474-1483页

作者： da Silveira, Juliano C. de Andrade, Gabriella M. Nogueira, Marcelo F. G. Meirelles, Flavio V. Perecin, Felipe Univ Sao Paulo Fac Anim Sci & Food Engn Dept Vet Med BR-13635900 Pirassununga SP Brazil Univ Sao Paulo State Fac Sci & Letters Dept Biol Sci Assis SP Brazil

Ovarian follicular development is a controlled series of events culminating with an ovulatory or atretic follicle. Micrornas (mirnas) are small noncoding rnas involved in translational regulation of genes in different developmental processes. Deletion of Dicer in mice ovaries demonstrated the importance of mirnas in reproduction, which led to infertility. The mirnas were thought to act only within host cells;however, these molecules are also present in cell-secreted vesicles. These vesicles are present in body fluids such as milk, serum, and ovarian follicular fluid. Vesicles are secreted in extracellular fluids and travel from donor to target cells, mediating transfer of bioactive material. Herein we discuss the role of hormonal-regulated mirnas within different ovarian follicular cells as well as cell-secreted vesicles participation in mammalian ovarian follicular fluid. Furthermore, we discuss the possibility of mirnas transference mediated by cell-secreted vesicles present in ovarian follicular fluid, increasing the versatility of mirna functions during antral follicle development.

关键词： follicle noncoding rna posttranscriptional gene regulation mirnas cell-secreted vesicles

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miRror2.0: A PLATFORM FOR ASSESSING THE JOINT ACTION OF MICROrnaS IN CELL REGULATION

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JOUrnaL OF BIOINFORMATICS AND COMPUTATIONAL BIOLOGY 2013年第6期11卷 1-15页

作者： Friedman, Yitzhak Linial, Michal Hebrew Univ Jerusalem Inst Life Sci Dept Biol Chem IL-91904 Jerusalem Israel

micrornas (mirnas) are short, noncoding rnas that negatively regulate the levels of mrna post-transcriptionally. Recent experiments revealed thousands of mrna-mirna pairs in which multiple mirnas may bind the same transcript. These results raised the notion of mirnas teamwork for a wide range of cellular context. miRror2.0 utilizes the mirna-target predictions from over a dozen programs and resources and unifies them under a common statistical basis. The platform, called miRror2.0, considers the combinatorial regulation by mirnas in different tissues, cell lines and under a broad range of conditions. A flexible setting permits the selection of the preferred combination of mirna-target prediction resources as well as the statistical parameters for the analysis. miRror2.0 covers six major model organisms including human and mouse. Importantly, the system is capable of analyzing hundreds of genes that were subjected to mirnas' regulation. Activating miRror2.0 by introducing thousands of genes from mirna overexpression experiments successfully identified the objective mirnas. The output from miRror2.0 is a list of genes that is optimally regulated by a defined set of mirnas. A symmetric application of miRror2.0 starts with a set of mirnas, and the system then seeks the preferred set of genes that are regulated by that mirna composition. The results from miRror2.0 are empowered by an iterative procedure called PSI-miRror. PSI-miRror tests the robustness of miRror2.0 prediction. It allows a refinement of the initial list of genes in view of the mirnas that optimally regulate this list. We present miRror2.0 as a valuable resource for supporting cellular experimentalists that seek recovery of combinatorial regulation by mirnas from noisy experimental data. miRror2.0 is available at http://***.

关键词： noncoding rna RISC microrna-target pair prediction tool combinatorial regulation StarBase PAR-CLIP miRBase

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Localization of rnas in the nucleus: cis- and trans- regulation

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rna BIOLOGY 2021年第12期18卷 2073-2086页

作者： Tong, Chong Yin, Yafei Zhejiang Univ Sch Med Affiliated Hosp 2 Dept Cell Biol Res Bldg C423 Hangzhou 310058 Zhejiang Peoples R China Zhejiang Univ Sch Med Affiliated Hosp 2 Dept Cardiol Res Bldg C423 Hangzhou 310058 Zhejiang Peoples R China

The subcellular localization of rnas correlates with their function and how they are regulated. Most protein-coding mrnas are exported into the cytoplasm for protein synthesis, while some mrna species, long noncoding rnas, and some regulatory element-associated unstable transcripts tend to be retained in the nucleus, where they function as a regulatory unit and/or are regulated by nuclear surveillance pathways. While the mechanisms regulating mrna export and localization have been well summarized, the mechanisms governing nuclear retention of rnas, especially of noncoding rnas, are seldomly reviewed. In this review, we summarize recent advances in the mechanistic study of rna nuclear retention, especially for noncoding rnas, from the angle of cis-acting elements embedded in rna transcripts and their interaction with trans-acting factors. We also try to illustrate the general principles of rna nuclear retention and we discuss potential areas for future investigation.

关键词： noncoding rna nuclear retention chromatin association u1 snRNP splicing hnrnpk repeat xist rna decay

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