scholarly journals Long noncoding RNA ANRIL protects cardiomyocytes against hypoxia/reoxygenation injury by sponging miR-195-5p and upregulating Bcl-2

RSC Advances ◽  
2019 ◽  
Vol 9 (61) ◽  
pp. 35624-35635 ◽  
Author(s):  
Hui Zhao ◽  
Li Meng ◽  
Chengyang Xu ◽  
Bin Lin ◽  
Xiangming Zheng ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Reoxygenation Injury ◽  
Hypoxia Reoxygenation

Long noncoding RNAs have been widely accepted to play important roles in acute myocardial infarction (AMI).

THU0078 EXPRESSION PROFILE ANALYSIS OF LONG NONCODING RNAS INDUCED BY IL-1ß IN RHEUMATOID ARTHRITIS FIBROBLAST-LIKE SYNOVIOCYTES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 251.1-251
Author(s):  
J. M. Kim ◽  
H. J. Kang ◽  
S. J. Jung ◽  
B. W. Song ◽  
H. J. Jeong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Expression Profile ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Aberrant Expression ◽  
Iκb Kinase ◽  
Ngs Data ◽  
Fibroblast Like Synoviocytes

Background:Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators and the aberrant expression of lncRNAs has been reported in various diseases including cancer, cardiovascular disease, and diabetes mellitus. However, the role of lncRNAs in the pathogenesis of rheumatoid arthritis (RA) remains unknown.Objectives:Thus, we studied lncRNAs influenced by IL-1, which is one of the key mediators in the pathogenesis of RA, and also investigated whether regulation of NF-κB activation, which is known to be induced by IL-1, could lead to the changes of expression of those lncRNAs.Methods:Fibroblast-like synoviocytes (FLS) were obtained from the knee joints of the patients with RA. The next-generation sequencing (NGS) data were analyzed to identify differentially expressed lncRNAs between unstimulated RA FLS and IL-1-stimulated RA FLS. The expression levels of the top 5 candidates in NGS data were validated by RT-qPCR using extended number of unstimulated RA FLS and IL-1-stimulated RA FLS. IMD-0560, an inhibitor of IκB kinase (IKK) was used for the regulation of NF-κB activation. Activation and inhibition of NF-κB were confirmed by Western blotting. Changed expressions of the lncRNAs were identified by RT-qPCR.Results:NGS analysis revealed up-regulated 30 lncRNAs and down-regulated 15 lncRNAs in IL-1-treated RA FLS compared with unstimulated RA FLS. Top 5 lncRNAs were selected among 30 lncRNAs up-regulated by IL-1 in RA FLS based on fold-change with P-value cutoff. The up-regulated lncRNAs including NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 were validated by RT-qPCR. IMD-0560 inhibited phosphorylation of IκBα induced by IL-1 in RA FLS. Overexpression of lncRNAs induced by IL-1 was also inhibited by IMD-0560 in RA FLS.Conclusion:Our study revealed that IL-1 increased the expression of NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 in RA FLS. In addition, the expression of these lncRNAs was regulated by inhibition of NF-κB activation. Thus, our data suggest that the lncRNAs might be involved in the pathogenesis of RA through NF-κB signaling pathway.References:[1]Long noncoding RNAs and human disease. Trends Cell Biol. 2011 Jun;21(6):354-61.[2]A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16;341(6147):789-92.[3]Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Res Ther. 2016 Oct 6;18(1):227.Disclosure of Interests:None declared

Experimental and population-genetic evidence for inflammation control functions of long noncoding RNAs and a novel tRNA-like transcript arising from the human NEAT1-MALAT1 genomic region

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Poller ◽  
A.W Kuss ◽  
S Weiss ◽  
A Haghikia ◽  
M Gast ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Gene Cluster ◽  
Immune Cells ◽  
Noncoding Rna ◽  
Disease Patient ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Funding Source ◽  
Control Functions ◽  
Interleukin Receptors

Abstract Background Uncontrolled inflammation is a key driver of atherosclerosis, myocardial infarction (MI), and multiple other diseases. Beyond proteins and microRNAs, long noncoding RNAs (lncRNAs) are implicated in inflammation control. We previously reported suppression of lncRNA NEAT1 in circulating immune cells of post-MI patients. In mice lacking lncRNAs NEAT1 or MALAT1 we observed major immune disturbances affecting monocyte-macrophage and T cell differentiation and rendering the immune system unstable and highly vulnerable to immune stress. Here, we report functions of a novel tRNA-type transcript arising from the NEAT1-MALAT1 gene cluster, and on genetic heterogeneity of this region in the human population. Methods and results While previously investigated mice were deficient in the entire NEAT1 or MALAT1 locus, we here aimed to selectively disrupted only the novel 59-nt tRNA-like transcript “menRNA” with hitherto unknown functions. Through CRISPR/Cas9 editing we developed 4 human THP-1 monocyte-macrophage cell line clones with deletions of different extension all of which prevented, however, normal transcript folding and formation of “menRNA”. Transcriptome mapping of all clones by RNA-sequencing identified dysregulation of innate immunity-related genes (IFI16, IFITM3, IRAK3, IRF2BP2, IRF3), chemokine and interleukin receptors (CCR10, IL11RA, IL12RB2, IL23A), cell surface receptors (CD37, CD40LG, CD72, FOCAD, ITGA6, MAEA, THY1), macrophage function-associated genes (ELANE, GRN, MIF, MMP25, MST1P2, PRTN3), tRNA-processing transcripts (GARS, QRSL1P3, QTRT1P1, THG1L, VARS), and small nucleolar RNAs (SNORA26.62.64, SNORD65.112). These data and functional assays indicate functions of NEAT1-derived “menRNA” distinct from those previously described for MALAT1-derived mascRNA. As multiple data suggest inflammation control functions of the NEAT1-MALAT1 region, we investigated the extent of genetic variability of this region in humans. In cohorts from the SHIP study coordinated by the Institute for Community Medicine Greifswald, screening of this region for sequence variants and possible phenotype associations was conducted the results of which are given in Figure 1. Consistent with prior findings, a MALAT1 SNP with very low minor allele frequency (MAF=0.01) was associated (p=0.0062) with systemic low level inflammation (CRP >3.0 mg/L). Unexpected was the association (p<0.01) of eight SNPs (low MAF=0.09 for all) with BMI >35 kg/m2 and LDL >164 mg/dl. Conclusions First, selective disruption of menRNA formation in human monocyte-macrophages provides evidence that this novel type of noncoding RNA has immunoregulatory functions. Second, the phenotype associations of SNPs within the NEAT1-MALAT1 gene cluster warrant further in-depth investigation of the molecular basis of these associations, and of their allele frequencies in cardiovascular disease patient cohorts. The first three and the last authors contributed equally to this work. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): “Transcriptome analysis of circulating immune cells to improve the assessment of prognosis and the response to novel anti-inflammatory treatments after myocardial infarction”; DZHK Shared Expertise project B19-006_SE FKZ 81X2100257

scholarly journals Long Noncoding RNA Plays a Key Role in Metastasis and Prognosis of Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Guangbing Li ◽  
Haohai Zhang ◽  
Xueshuai Wan ◽  
Xiaobo Yang ◽  
Chengpei Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Comprehensive Review ◽  
Cellular Processes

Long noncoding RNAs (lncRNAs) have been attracting immense research interests. However, only a handful of lncRNAs had been thoroughly characterized. They were involved in fundamental cellular processes including regulation of gene expression at epigenetics as well as tumorogenesis. In this paper, we give a systematic and comprehensive review of existing literature about lncRNA involvement in hepatocellular carcinoma. This review exhibited that lncRNAs played important roles in tumorigenesis and subsequent prognosis and metastasis of hepatocellular carcinoma and elucidated the role of some specific lncRNAs such as MALAT1 and HOTAIR in the pathophysiology of hepatocellular carcinoma and their potential of being therapeutic targets.

Long Noncoding RNAs in Patients With Acute Myocardial Infarction

2014 ◽  
Vol 115 (7) ◽  
pp. 668-677 ◽  
Author(s):  
Mélanie Vausort ◽  
Daniel R. Wagner ◽  
Yvan Devaux
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas

scholarly journals A new cancer-testis long noncoding RNA, the OTP-AS1 RNA

2018 ◽  
Author(s):  
Iuliia K. Karnaukhova ◽  
Dmitrii E. Polev ◽  
Larisa L. Krukovskaya ◽  
Alexey E. Masharsky ◽  
Olga V. Nazarenko ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Protein Coding ◽  
Regulatory Interactions ◽  
Normal Tissues ◽  
Non Coding Rnas ◽  
Cancer Testis

AbstractOrthopedia homeobox (OTP) gene encodes a homeodomain-containing transcription factor involved in brain development. OTP is mapped to human chromosome 5q14.1. Earlier we described transcription in the second intron of this gene in wide variety of tumors, but among normal tissues only in testis. In GeneBank these transcripts are presented by several 300-400 nucleotides long AI267901-like ESTs.We assumed that AI267901-like ESTs belong to longer transcript(s). We used the Rapid Amplification of cDNA Ends (RACE) approach and other methods to find the full-length transcript. The found transcript was 2436 nucleotides long polyadenylated sequence in antisense to OTP gene. The corresponding gene consisted of two exons separated by an intron of 2961 bp long. The first exon was found to be 91 bp long and located in the third exon of OTP gene. The second exon was 2345bp long and located in the second intron of OTP gene.The search of possible open reading frames (ORFs) showed the lack of significant ORFs. We have shown the expression of new gene in many human tumors and only in one sampled normal testis. The data suggest that we discovered a new antisense cancer-testis sequence OTP-AS1 (OTP- antisense RNA 1), which belongs to long noncoding RNAs (lncRNAs). According to our findings we assume that OTP-AS1 and OTP genes may be the CT-coding gene/CT-ncRNA pair involved in regulatory interactions.Author summaryPreviously, long non-coding RNAs (lncRNAs) were considered as genetic “noise”. However, it was later shown that only 2% of genomic transcripts have a protein-coding ability. Non-coding RNA is divided into short non-coding RNAs (20-200 nucleotides) and long noncoding RNAs (200-100,000 nucleotides). Genes encoding lncRNA often overlap or are adjacent to protein-coding genes, and localization of this kind is beneficial in order to regulate the transcription of neighboring genes. Studies have shown that of lncRNAs play many roles in the regulation of gene expression. New evidence indicates that dysfunctions of lncRNAs are associated with human diseases and cancer.In our study we found a new cancer-testis long noncoding RNA (OTP-AS1), which is an antisense of protein-coding cancer-testis gene (OTP). Thus, OTP-AS1 and OTP genes may be the CT-coding gene/CT-ncRNA pair involved in regulatory interactions. This is supported by the similar profile of their expression. OTP-AS1 may be of interest as a potential diagnostic marker of cancer or a potential target for cancer therapy.Part of OTP-AS1 gene (5’-end of the second exon) is evolutionary younger than the rest of gene sequence and is less conservative. This links OTP-AS1 gene with so-called TSEEN (tumor-specifically expressed, evolutionary novel) genes described by the authors in previous papers.

scholarly journals Transvection and pairing of a Drosophila Hox long noncoding RNA in the regulation of Sex combs reduced

2016 ◽  
Author(s):  
Tom Pettini ◽  
Matthew Ronshaugen
Keyword(s):  
Gene Expression ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Early Embryo ◽  
Long Noncoding Rnas ◽  
Regulatory Sequences ◽  
Sex Combs Reduced ◽  
Hox Gene ◽  
Sex Combs

ABSTRACTLong noncoding RNAs have emerged as abundant and important regulators of gene expression in diverse animals. In D. melanogaster several lncRNAs involved in regulating Hox gene expression in the Bithorax Complex have been reported. However, no functional Hox long noncoding RNAs have been described in the Antennapedia Complex. Here we have characterized a long noncoding RNA lincX from the Antennapedia Complex, that is transcribed from previously identified cis-regulatory sequences of the Hox gene Sex combs reduced (Scr). We use both the GAL4-UAS system and mutants to ectopically overexpress the lincX RNA from exogenous and endogenous loci respectively, in order to dissect the potential regulatory functions of lincX RNA versus lincX transcription. Our findings suggest that transcription through the lincX locus, but not the lincX RNA itself, may facilitate initiation of Scr in cis in the early embryo. Transvection phenomena, where regulatory sequences on one chromosome can affect expression on the homolog, have previously been reported in genetic studies of Scr. By analysing lincX and Scr nascent transcriptional sites in embryos heterozygous for a gain of function mutation, we directly visualize this transvection, and observe that the ectopic lincX transcriptional state appears to be relayed in trans to the homologous wild-type chromosome. This trans-activation of lincX correlates with both ectopic activation of Scr in cis, and increased chromosomal proximity. Our results are consistent with a model whereby early long noncoding RNA transcription through cis-regulatory sequences can be communicated between chromosomes, and facilitates long-range initiation of Hox gene expression in cis.

scholarly journals lncINS-IGF2 Promotes Cell Proliferation and Migration by Promoting G1/S Transition in Lung Cancer

2019 ◽  
Vol 18 ◽  
pp. 153303381882302 ◽  
Author(s):  
Shenglan Gao ◽  
Ziying Lin ◽  
Chunyan Li ◽  
Yahong Wang ◽  
Lawei Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Small Cell ◽  
Long Noncoding Rnas ◽  
Transcript Variant ◽  
Small Cell Lung

Long noncoding RNAs are capable of regulating gene expression at multiple levels. These RNA molecules are also involved in a variety of physiological and pathological processes. Emerging data demonstrate that a series of differentially expressed long noncoding RNAs are implicated in tumorigenesis. In the present study, we used microarray analysis to identify long noncoding RNAs that are dysregulated in non-small-cell lung cancer when compared to normal lung tissues. Accordingly, we performed quantitative real-time polymerase chain reaction to analyze the levels of long noncoding RNA and the cis target gene. We further found the oncogene property of long noncoding RNA that long noncoding RNA downexpression inhibits non-small-cell lung cancer cells proliferation and migration based on 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and colony formation assays and wound healing as well as transwell assays. The influence of long noncoding RNA on cell cycle of non-small-cell lung cancer cells is also analyzed by flow cytometry. Among the dysregulated long noncoding RNAs, we identified INS-IGF2 readthrough, transcript variant 1, noncoding RNA (NR_003512.3) is upregulated in non-small-cell lung cancer tissues, the cis gene of which is insulin-like growth factor 2 gene hinted by bioinformatics analysis. We also observed that downregulation of INS-IGF2 readthrough, transcript variant 1, noncoding RNA reduces insulin-like growth factor 2 messenger RNA expression. Furthermore, INS-IGF2 readthrough, transcript variant 1, noncoding RNA downregulation suppresses non-small-cell lung cancer cell proliferation and migration. This downregulation results in a concomitant inhibition of the G1/S transition in non-small-cell lung cancer cells. Our findings suggest that INS-IGF2 readthrough, transcript variant 1, noncoding RNA may be an oncogene involved in the development of lung cancer. Therefore, we speculate that INS-IGF2 readthrough, transcript variant 1, noncoding RNA represents a potential therapeutic target for lung cancer.

scholarly journals Long noncoding RNA ANRIL knockdown increases sensitivity of non-small cell lung cancer to cisplatin by regulating the miR-656-3p/SOX4 axis

RSC Advances ◽  
2019 ◽  
Vol 9 (66) ◽  
pp. 38735-38744
Author(s):  
Xianfang Wang ◽  
Jun Shi ◽  
Ying Chen ◽  
Caihong Wang ◽  
Huifang Shi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Small Cell ◽  
Long Noncoding Rnas ◽  
Small Cell Lung

Long noncoding RNAs (lncRNAs) are implicated in the development of chemoresistance in many cancers.

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