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Gene expression profile and long non-coding rna analysis, using rna-Seq, in chicken embryonic fibroblast cells infected by avian leukosis virus J

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ARCHIVES OF VIROLOGY 2018年第3期163卷 639-647页

作者： Hu, Xuming Chen, Shihao Jia, Chongxin Xue, Songlei Dou, Chunfeng Dai, Zhenqing Xu, Hui Sun, Zhen Geng, Tuoyu Cui, Hengmi Yangzhou Univ Inst Epigenet & Epigen Coll Anim Sci & Technol 48 East Wenhui Rd Yangzhou 225009 Jiangsu Peoples R China Jiangsu Coinnovat Ctr Prevent & Control Important Yangzhou 225009 Jiangsu Peoples R China Yangzhou Univ Inst Comparat Med Yangzhou 225009 Jiangsu Peoples R China Yangzhou Univ Joint Int Res Lab Agr & Agriprod Safety Yangzhou 225009 Jiangsu Peoples R China

Avian leukosis virus J (ALVJ) infection induces hematopoietic malignancy in myeloid leukemia and hemangioma in chickens. However, little is known about the mechanisms underpinning the unique pathogenesis of ALVJ. In this study, we investigated the gene expression profiles of ALVJ-infected chicken cells and performed a comprehensive analysis of the long non-coding rnas (lncrnas) in CEF cells using rna-Seq. As a result, 36 differentially expressed lncrnas and 91 genes (FC > 2 and q-values < 0.05) were identified. Bioinformatics analysis revealed that these differentially expressed genes are involved in the innate immune response. Target prediction analysis revealed that these lncrnas may act in cis or trans and affect the expression of genes which are involved in the anti-viral innate immune responses. Toll-like receptor, RIG-I receptor, NOD-like receptor and JAK-STAT signaling pathways were enriched. Notably, the induced expression of innate immunity genes, including B2M, DHX58, IFI27L2, IFIH1, IRF10, ISG12(2), MX, OAS*A, RSAD2, STAT1, TLR3, IL4I1, and IRF1 (FC > 2 and correlation > 0.95), were highly correlated with the upregulation of several lncrnas, including MG066618, MG066617, MG066601, MG066629, MG066609 and MG066616. These findings identify the expression profile of lncrnas in chicken CEF cells infected by ALVJ virus and provide new insights into the molecular mechanisms of ALVJ infection.

关键词： non-coding rna AVIAN leukosis LEUKEMIA in animals MYELOID leukemia genetics CHICKEN genetics GENETIC aspects

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CHIR99021 promotes self-renewal of mouse embryonic stem cells by modulation of protein-encoding gene and long intergenic non-coding rna expression

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EXPERIMENTAL CELL RESEARCH 2013年第17期319卷 2684-2699页

作者： Wu, Yongyan Ai, Zhiying Yao, Kezhen Cao, Lixia Du, Juan Shi, Xiaoyan Guo, Zekun Zhang, Yong Northwest A&F Univ Coll Vet Med Yangling 712100 Shaanxi Peoples R China Northwest A&F Univ Key Lab Anim Biotechnol Minist Agr Yangling 712100 Shaanxi Peoples R China Northwest A&F Univ Coll Life Sci Yangling 712100 Shaanxi Peoples R China

Embryonic stem cells (ESCs) can proliferate indefinitely in vitro and differentiate into cells of all three germ layers. These unique properties make them exceptionally valuable for drug discovery and regenerative medicine. However, the practical application of ESCs is limited because it is difficult to derive and culture ESCs. It has been demonstrated that CHIR99021 (CHIR) promotes self-renewal and enhances the derivation efficiency of mouse (m)ESCs. However, the downstream targets of CHIR are not fully understood. In this study, we identified CHIR-regulated genes in mESCs using microarray analysis. Our microarray data demonstrated that CHIR not only influenced the Wnt/beta-catenin pathway by stabilizing beta-catenin, but also modulated several other pluripotency-related signaling pathways such as TGF-beta, Notch and MAPK signaling pathways. More detailed analysis demonstrated that CHIR inhibited Nodal signaling, while activating bone morphogenetic protein signaling in mESCs. In addition, we found that pluripotency-maintaining transcription factors were Up-regulated by CHIR, while several developmental-related genes were down-regulated. Furthermore, we found that CHIR altered the expression of epigenetic regulatory genes and long intergenic non-coding rnas. Quantitative real-time PCR results were consistent with microarray data, suggesting that CHIR alters the expression pattern of protein-encoding genes (especially transcription factors), epigenetic regulatory genes and non-coding rnas to establish a relatively stable pluripotency-maintaining network. (C) 2013 Elsevier Inc. All rights reserved.

关键词： Embryonic stem cells CHIR99021 Microarray Nodal signaling BMP signaling non-coding rna

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A host non-coding rna, nc886, plays a pro-viral role by promoting virus trafficking to the nucleus

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MOLECULAR THERAPY-ONCOLYTICS 2022年 24卷 683-694页

作者： Saruuldalai, Enkhjin Park, Jiyoung Kang, Dongmin Shin, Seung-Phil Im, Wonkyun Ronny Lee, Hwi-Ho Jang, Jiyoung Joan Park, Jong-Lyul Kim, Seon-Young Hwang, Jung-Ah Kim, Young-Dong Lee, Jung-Hoon Park, Eun Jung Lee, Yeon-Su Kim, In-Hoo Lee, Sang-Jin Lee, Yong Sun Natl Canc Ctr Grad Sch Canc Sci & Policy Dept Canc Biomed Sci Goyang 10408 South Korea Ewha Womans Univ Dept Life Sci Fluorescence Core Imaging Ctr Seoul 03760 South Korea Natl Canc Ctr Res Inst Div Canc Immunol Goyang 10408 South Korea KRIBB Personalized Genom Med Res Ctr Daejeon 34141 South Korea Univ Sci & Technol Dept Funct Genom Daejeon 34113 South Korea Natl Canc Ctr Res Inst Res Core Ctr Genom Core Facil Goyang 10408 South Korea Hallym Univ Dept Life Sci Chunchon 24252 South Korea Hallym Univ Multidisciplinary Genome Inst Chunchon 24252 South Korea Natl Canc Ctr Res Inst Div Clin Canc Res Goyang 10408 South Korea

Elucidation of the interplay between viruses and host cells is crucial for taming viruses to benefit human health. Cancer therapy using adenovirus, called oncolytic virotherapy, is a promising treatment option but is not robust in all patients. In addition, inefficient replication of human adenovirus in mouse hampered the development of an in vivo model for preclinical evaluation of therapeutically engineered adenovirus. nc886 is a human non-coding rna that suppresses Protein Kinase R (PKR), an antiviral protein. In this study, we have found that nc886 greatly promotes adenoviral gene expression and replication. Remarkably, the stimulatory effect of nc886 is not dependent on its function to inhibit PKR. Rather, nc886 facilitates the nuclear entry of adenovirus via modulating the kinesin pathway. nc886 is not conserved in mouse and, when xenogeneically expressed in mouse cells, promotes adenovirus replication. Our investigation has discovered a novel mechanism of how a host ncrna plays a pro-adenoviral role. Given that nc886 expression is silenced in a subset of cancer cells, our study highlights that oncolytic virotherapy might be inefficient in those cells. Furthermore, our findings open future possibilities of harnessing nc886 to improve the efficacy of oncolytic adenovirus and to construct nc886-expressing transgenic mice as an animal model.

关键词： nc886 adenovirus kinesin oncolytic virotherapy non-coding rna host tropism Protein Kinase R

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Ntab, a novel non-coding rna abundantly expressed in rat brain

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NEUROSCIENCE 2001年第2期108卷 207-215页

作者： French, PJ Bliss, TVP O'Connor, V Erasmus Univ Dept Anat Inst Neurosci NL-3000 DR Rotterdam Netherlands Natl Inst Med Res Neurophysiol Div London NW7 1AA England

We have identified a novel transcript that is abundantly and specifically expressed in both the adult and developing rat CNS. Within the full-length cDNA sequence we were unable to identify a clear open reading frame. Moreover, we were unable to detect any protein product derived from the full-length cDNA sequence using an in vitro translation assay. Therefore, we suggest this gene is one of a growing number of non-coding mrna-like rna transcripts that exert their cellular functions directly as an rna. We have named this novel gene Ntab for non-coding transcript abundantly expressed in brain (accession number AY035551). In addition, in some regions of the brain we find evidence for rna accumulation in cellular processes at some distance from the soma. These findings suggest that Ntab is actively transported and may function within cellular processes. Since Ntab is a targeted non-coding rna, such Cellular functions could include the targeting and/or regulation of localised translation of other mrna species. (C) 2001 IBRO, Published by Elsevier Science Ltd. All rights reserved.

关键词： neural gene expression non-coding rna rna targeting cerebellum

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Small non-coding rna profiling and the role of pirna pathway genes in the protection of chicken primordial germ cells

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BMC GENOMICS 2014年第1期15卷 1-15页

作者： Rengaraj, Deivendran Lee, Sang In Park, Tae Sub Lee, Hong Jo Kim, Young Min Sohn, Yoon Ah Jung, Myunghee Noh, Seung-Jae Jung, Hojin Han, Jae Yong Seoul Natl Univ Dept Agr Biotechnol Coll Agr & Life Sci Seoul 151921 South Korea Seoul Natl Univ Res Inst Agr & Life Sci Coll Agr & Life Sci Seoul 151921 South Korea Chung Ang Univ Dept Anim Sci & Technol Anseong 456756 South Korea Seoul Natl Univ Grad Sch Int Agr Technol Pyeongchang Gun 232916 Gangwon Do South Korea Seoul Natl Univ Inst Green Bio Sci & Technol Pyeongchang Gun 232916 Gangwon Do South Korea Insilicogen Inc Codes Div Suwon 441813 South Korea

Background: Genes, rnas, and proteins play important roles during germline development. However, the functions of non-coding rnas (ncrnas) on germline development remain unclear in avian species. Recent high-throughput techniques have identified several classes of ncrnas, including micro rnas (mirnas), small-interfering rnas (sirnas), and PIWI-interacting rnas (pirnas). These ncrnas are functionally important in the genome, however, the identification and annotation of ncrnas in a genome is challenging. The aim of this study was to identify different types of small ncrnas particularly pirnas, and the role of pirna pathway genes in the protection of chicken primordial germ cells (PGCs). Results: At first, we performed next-generation sequencing to identify ncrnas in chicken PGCs, and we performed ab initio predictive analysis to identify putative pirnas in PGCs. Then, we examined the expression of three repetitive sequence-linked pirnas and 14 genic-transcript-linked pirnas along with their linked genes using real-time PCR. All pirnas and their linked genes were highly expressed in PGCs. Subsequently, we knocked down two known pirna pathway genes of chicken, PIWI-like protein 1 (CIWI) and 2 (CILI), in PGCs using sirnas. After knockdown of CIWI and CILI, we examined their effects on the expression of six putative pirna-linked genes and DNA double-strand breakage in PGCs. The knockdown of CIWI and CILI upregulated chicken repetitive 1 (CR1) element and RAP2B, a member of RAS oncogene family, and increased DNA double-strand breakage in PGCs. Conclusions: Our results increase the understanding of PGC-expressed pirnas and the role of pirna pathway genes in the protection of germ cells.

关键词： Aves non-coding rna pirna Primordial Germ Cells

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INTErnaTIONAL JOUrnaL OF GENERAL MEDICINE 2021年 14卷 6621-6637页

作者： Liu, Boxuan Zhao, Yun Yang, Shuanying Xi An Jiao Tong Univ Affiliated Hosp 2 Dept Crit Care & Resp Med 157 Xiwu Rd Xian 710004 Shaanxi Peoples R China Xi An Jiao Tong Univ Affiliated Hosp 1 Dept Cardiol Xian 710004 Shaanxi Peoples R China

Purpose: Lung cancer is the most common and deadly cancer type affecting humans. Although huge progress has been made on early diagnosis and precision treatment, the overall 5 year survival rate remains low. In this study, we constructed an autophagyrelated long non-coding rna (lncrna) prognostic signature for guiding clinical practice. Methods: From The Cancer Genome Atlas, we retrieved mrna and lncrna expression matrices of patients with lung squamous carcinoma. We then established a prognostic risk model using Lasso regression and multivariate Cox regression. The model generated a risk score to differentiate high-and low-risk groups. An ROC curve and nomogram were used to visualize the predictive ability of the current signatures. Finally, we used Gene Set Enrichment Analysis to determine gene ontology and pathway enrichment. Results: After screening 1248 autophagy-related lncrnas, we selected seven lncrnas (LUCAT1, AC022150.2, AL035425.3, AC138976.2, AC106786.1, GPRC5D-AS1 and AP006545.2) for our signature. Univariate (hazard ratio [HR] = 2.147, 95% confidence interval [CI]: 1.681-2.743, P < 0.001) and multivariate (HR = 2.096, 95% CI: 1.652- 2.658, P < 0.001) Cox regression analyses revealed that the risk score is an independent predictive factor for LUSC patients. Further, areas under the receiver operating characteristic curve were 0.622, 0.699, and 0.721, respectively, for the 1 year, 3 year, and 5 year risk scores-indicating a reliable model. Selected lncrnas were primarily enriched in autophagy, metabolism, MAPK pathway, and JAK/STAT pathway. Further drug sensitivity analysis revealed that low-risk patients were more sensitive to Cisplatin, Docetaxel, Vinblastine, and Vinorelbine. Finally, a multiomics analysis found that lncrna-linked proteins IKBKB and SQSTM1 were expressed at low levels and significantly correlated in tumor samples, compared with normal tissue. Conclusion: Our prognostic model successfully predicted patient prognosis in lung cancer.

关键词： non-small cell lung cancer cancer therapy non-coding rna cancer prognosis The Cancer Genome Atlas

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The pluripotent role of exosomes in mediating non -coding rna in ventricular remodeling after myocardial infarction

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LIFE SCIENCES 2020年第0期254卷 117761-117761页

作者： Qi, Zhongwen Wu, Dan Li, Meng Yan, Zhipeng Yang, Xiaoya Ji, Nan Wang, Yueyao Zhang, Junping Tianjin Univ Tradit Chinese Med Teaching Hosp 1 Tianjin 300183 Peoples R China Tianjin Univ Tradit Chinese Med Grad Sch Tianjin 300193 Peoples R China

With the increase of an aging population and the rising incidence of cardiovascular diseases, heart failure (HF) patients are on the rise every year. Myocardial infarction (MI) is the leading cause of HF in patients among cardiovascular diseases. In clinic, patients with MI are often assessed by biochemical indicators, electrocardiography, brain natriuretic peptide levels, myocardial enzymology, echocardiography and other means to predict the occurrence of HF and ventricular remodeling (VR). But there is still a lack of more accurate evaluation. VR is the basic mechanism of HF. In recent years, the molecular mechanism of VR has been studied mainly from the aspects of myocardial hypertrophy, myocardial fibrosis, inflammation, myocardial energy disorder, apoptosis, autophagy and pyroptosis. Exosomes are considered as the main mediators of intercellular information transmission. In addition, exosomes can promote the migration and transformation of intercellular rnas, which are highly conserved non-coding rnas. They can mediate the process of cell proliferation and differentiation of the target cell membrane. Exosomes have protective effects on VR after MI by inhibiting fibrosis, promoting angiogenesis and inhibiting inflammation and pyroptosis. We reviewed the specific protective mechanisms of exosomes for VR after MI. In addition, we discussed the formation of targeted exosomes and the role of non-coding rnas in VR.

关键词： Myocardial Infarction Ventricular remodeling Targeted exosomes non-coding rna Function and treatment

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Expression of a non-coding rna in ectromelia virus is required for normal plaque formation

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VIRUS GENES 2014年第1期48卷 38-47页

作者： Esteban, David J. Upton, Chris Bartow-McKenney, Casey Buller, R. Mark L. Chen, Nanhai G. Schriewer, Jill Lefkowitz, Elliot J. Wang, Chunlin Vassar Coll Dept Biol Poughkeepsie NY 12601 USA Univ Victoria Dept Biochem & Microbiol Victoria BC Canada St Louis Univ Dept Mol Microbiol & Immunol St Louis MO 63103 USA Genelux Corp San Diego Sci Ctr San Diego CA USA Univ Alabama Birmingham Dept Microbiol Birmingham AL 35294 USA

Poxviruses are dsDNA viruses with large genomes. Many genes in the genome remain uncharacterized, and recent studies have demonstrated that the poxvirus transcriptome includes numerous so-called anomalous transcripts not associated with open reading frames. Here, we characterize the expression and role of an apparently non-coding rna in orthopoxviruses, which we call viral hairpin rna (vhrna). Using a bioinformatics approach, we predicted expression of a transcript not associated with an open reading frame that is likely to form a stem-loop structure due to the presence of a 21 nt palindromic sequence. Expression of the transcript as early as 2 h post-infection was confirmed by northern blot and analysis of publicly available vaccinia virus infected cell transcriptomes. The transcription start site was determined by RACE PCE and transcriptome analysis, and early and late promoter sequences were identified. Finally, to test the function of the transcript we generated an ectromelia virus knockout, which failed to form plaques in cell culture. The important role of the transcript in viral replication was further demonstrated using sirna. Although the function of the transcript remains unknown, our work contributes to evidence of an increasingly complex poxvirus transcriptome, suggesting that transcripts such as vhrna not associated with an annotated open reading frame can play an important role in viral replication.

关键词： Ectromelia virus Vaccinia virus non-coding rna Stem-loop Plaques

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The progress, prospects, and challenges of the use of non-coding rna for diabetic wounds

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MOLECULAR THERAPY-NUCLEIC ACIDS 2021年 24卷 554-578页

作者： Li, Jianyi Wei, Miaomiao Liu, Xin Xiao, Shune Cai, Yuan Li, Fang Tian, Jiao Qi, Fang Xu, Guangchao Deng, Chengliang Zunyi Med Univ Dept Plast Surg Affiliated Hosp 149 Dalian Rd Zunyi 563000 Guizhou Peoples R China Affiliated Zunyi Med Univ Collaborat Innovat Ctr Tissue Injury Repair & Reg Zunyi 563000 Guizhou Peoples R China

Chronic diabetic wounds affect the quality of life of patients, resulting in significant social and economic burdens on both individuals and the health care system. Although treatment methods for chronic diabetic wounds have been explored, there remains a lack of effective treatment strategies;therefore, alternative strategies must be explored. Recently, the abnormal expression of non-coding rna in diabetic wounds has received widespread attention since it is an important factor in the development of diabetic wounds. This article reviews the regulatory role of three common non-coding rnas (microrna [mirna], long non-coding rna [lncrna], and circular rna [circrna]) in diabetic wounds and discusses the diagnosis, treatment potential, and challenges of non-coding rna in diabetic wounds. This article provides insights into new strategies for diabetic wound diagnosis and treatment at the genetic and molecular levels.

关键词： diabetic wound non-coding rna mirna lncrna circrna

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ncRDense: A novel computational approach for classification of non-coding rna family by deep learning

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GENOMICS 2021年第5期113卷 3030-3038页

作者： Chantsalnyam, Tuvshinbayar Siraj, Arslan Tayara, Hilal Chong, Kil To Jeonbuk Natl Univ Dept Elect & Informat Engn Jeonju 54896 South Korea Jeonbuk Natl Univ Sch Int Engn & Sci Jeonju 54896 South Korea Jeonbuk Natl Univ Adv Elect & Informat Res Ctr Jeonju 54896 South Korea

With the rapidly growing importance of biological research, non-coding rnas (ncrna) attract more attention in biology and bioinformatics. They play vital roles in biological processes such as transcription and translation. Classification of ncrnas is essential to our understanding of disease mechanisms and treatment design. Many approaches to ncrna classification have been developed, several of which use machine learning and deep learning. In this paper, we construct a novel deep learning-based architecture, ncRDense, to effectively classify and distinguish ncrna families. In a comparative study, our model produces comparable results with existing state-of-the-art methods. Finally, we built a freely accessible web server for the ncRDense tool, which is available at http://***/tools/ncRDense/.

关键词： Deep learning Densenet Classification non-coding rna Feature encoding

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