Genome-wide discovery and characterization of long noncoding RNAs in patients with multiple myeloma

Abstract Background Long noncoding RNAs (lncRNAs) are involved in a wide range of biological processes in tumorigenesis. However, the role of lncRNA expression in the biology, prognosis, and molecular classification of human multiple myeloma (MM) remains unclear, especially the biological functions of the vast majority of lncRNAs. Recently, lncRNAs have been identified in neoplastic hematologic disorders. Evidence has accumulated on the molecular mechanisms of action of lncRNAs, providing insight into their functional roles in tumorigenesis. This study aimed to characterize potential lncRNAs in patients with MM. Methods In this study, the whole-transcriptome strand-specific RNA sequencing of samples from three newly diagnosed patients with MM was performed. The whole transcriptome, including lncRNAs, microRNAs, and mRNAs, was analyzed. Using these data, MM lncRNAs were systematically analyzed, and the lncRNAs involved in the occurrence of MM were identified. Results The results revealed that MM lncRNAs had distinctive characteristics different from those of other malignant tumors. Further, the functions of a set of lncRNAs preferentially expressed in MM were verified, and several lncRNAs were identified as competing endogenous RNAs. More importantly, the aberrant expression of certain lncRNAs, including maternally expressed gene3, colon cancer–associated transcript1, and coiled-coil domain-containing 26, as well as some novel lncRNAs involved in the occurrence of MM was established. Further, lncRNAs were related to some microRNAs, regulated each other, and participated in MM development. Conclusions Genome-wide screening and functional analysis enabled the identification of a set of lncRNAs involved in the occurrence of MM. The interaction exists among microRNAs and lncRNAs.

Download Full-text

Transcriptome Analysis of Long Noncoding RNAs in Toll-Like Receptor 3-Activated Mesenchymal Stem Cells

Stem Cells International ◽

10.1155/2016/6205485 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Shihua Wang ◽

Xiaoxia Li ◽

Robert Chunhua Zhao

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Length Distribution ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Differentially Expressed ◽

Therapeutic Effects ◽

Wide Range

Mesenchymal stem cells (MSCs) possess great immunomodulatory capacity which lays the foundation for their therapeutic effects in a variety of diseases. Recently, toll-like receptors (TLR) have been shown to modulate MSC functions; however, the underlying molecular mechanisms are poorly understood. Emerging evidence suggests that long noncoding RNAs (lncRNAs) are an important class of regulators involved in a wide range of biological processes. To explore the potential involvement of lncRNAs in TLR stimulated MSCs, we performed a comprehensive lncRNA and mRNA profiling through microarray. 10.2% of lncRNAs (1733 out of 16967) and 15.1% of mRNA transcripts (1760 out of 11632) were significantly differentially expressed (absolute fold-change≥5 ,Pvalue≤0.05) in TLR3 stimulated MSCs. Furthermore, we characterized the differentially expressed lncRNAs through their classes and length distribution and correlated them with differentially expressed mRNA. Here, we are the first to determine genome-wide lncRNAs expression patterns in TLR3 stimulated MSCs by microarray and this work could provide a comprehensive framework of the transcriptome landscapes of TLR3 stimulated MSCs.

Download Full-text

Roles of long noncoding RNAs in Hepatocellular Carcinoma

Open Life Sciences ◽

10.1515/biol-2016-0012 ◽

2016 ◽

Vol 11 (1) ◽

pp. 91-97 ◽

Cited By ~ 3

Author(s):

Diyu Huang ◽

Jie Fang ◽

Gaojian Luo

Keyword(s):

Hepatocellular Carcinoma ◽

Mrna Stability ◽

Target Genes ◽

Rna Binding ◽

Rna Binding Proteins ◽

Malignant Tumors ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Aberrant Expression ◽

Comprehensive Review

AbstractLong noncoding RNAs (lncRNAs) are nonprotein coding transcripts longer than 200 nucleotides. Aberrant expression of lncRNAs has been found to be associated with hepatocellular carcinoma, one of the most malignant tumors. In this paper, we give a systematic and comprehensive review of existing literature about the involvement of lncRNAs in hepatocellular carcinoma. To date, evidence suggests that a number of lncRNAs, including HEIH, H19, HOTAIR, MALAT1, and PVT1, may regulate the transcription of target genes by recruiting histone-modifying complexes. Under certain circumstances, lncRNAs form RNA-dsDNA triplexes. Certain lncRNAs, such as HULC, HOTAIR, H19, HOTTIP and PTENP1, exhibit their biological roles by associating with microRNAs (miRNAs). In addition, by complementary base pairing with mRNAs or forming complexes with RNA binding proteins (RBPs), lncRNA-ATB, MALAT1 and PCNA-AS1 may mediate mRNA stability and splicing. In conclusion, interactions with DNA, RNA and proteins appears to be involved in lncRNAs’ participation in tumorigenesis and developmental processes related to hepatocellular carcinoma.

Download Full-text

Long Noncoding RNAs and Their Therapeutic Promise in Diabetic Nephropathy

Nephron ◽

10.1159/000515422 ◽

2021 ◽

pp. 1-11

Author(s):

Juan D. Coellar ◽

Jianyin Long ◽

Farhad R. Danesh

Keyword(s):

Diabetic Nephropathy ◽

Large Scale ◽

Kidney Diseases ◽

Noncoding Rnas ◽

Therapeutic Targets ◽

Long Noncoding Rnas ◽

Biological Processes ◽

Aberrant Expression ◽

Genome Wide

Recent advances in large-scale RNA sequencing and genome-wide profiling projects have unraveled a heterogeneous group of RNAs, collectively known as long noncoding RNAs (lncRNAs), which play central roles in many diverse biological processes. Importantly, an association between aberrant expression of lncRNAs and diverse human pathologies has been reported, including in a variety of kidney diseases. These observations have raised the possibility that lncRNAs may represent unexploited potential therapeutic targets for kidney diseases. Several important questions regarding the functionality of lncRNAs and their impact in kidney diseases, however, remain to be carefully addressed. Here, we provide an overview of the main functions and mechanisms of actions of lncRNAs, and their promise as therapeutic targets in kidney diseases, emphasizing on the role of some of the best-characterized lncRNAs implicated in the pathogenesis and progression of diabetic nephropathy.

Download Full-text

Plant Long Noncoding RNAs: New Players in the Field of Post-Transcriptional Regulations

Non-Coding RNA ◽

10.3390/ncrna7010012 ◽

2021 ◽

Vol 7 (1) ◽

pp. 12

Author(s):

Camille Fonouni-Farde ◽

Federico Ariel ◽

Martin Crespi

Keyword(s):

Gene Expression ◽

Cellular Localization ◽

Molecular Mechanisms ◽

Gene Expression Regulation ◽

Large Fraction ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Genomic Research ◽

Protein Coding ◽

Wide Range

The first reference to the “C-value paradox” reported an apparent imbalance between organismal genome size and morphological complexity. Since then, next-generation sequencing has revolutionized genomic research and revealed that eukaryotic transcriptomes contain a large fraction of non-protein-coding components. Eukaryotic genomes are pervasively transcribed and noncoding regions give rise to a plethora of noncoding RNAs with undeniable biological functions. Among them, long noncoding RNAs (lncRNAs) seem to represent a new layer of gene expression regulation, participating in a wide range of molecular mechanisms at the transcriptional and post-transcriptional levels. In addition to their role in epigenetic regulation, plant lncRNAs have been associated with the degradation of complementary RNAs, the regulation of alternative splicing, protein sub-cellular localization, the promotion of translation and protein post-translational modifications. In this review, we report and integrate numerous and complex mechanisms through which long noncoding transcripts regulate post-transcriptional gene expression in plants.

Download Full-text

Genome-Wide Identification and Characterization of Long Noncoding RNAs Involved in Chinese Wheat Mosaic Virus Infection of Nicotiana benthamiana

Biology ◽

10.3390/biology10030232 ◽

2021 ◽

Vol 10 (3) ◽

pp. 232

Author(s):

Weiran Zheng ◽

Haichao Hu ◽

Qisen Lu ◽

Peng Jin ◽

Linna Cai ◽

...

Keyword(s):

Virus Infection ◽

Mosaic Virus ◽

Nicotiana Benthamiana ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Differentially Expressed ◽

Genome Wide ◽

Chinese Wheat

Recent studies have shown that a large number of long noncoding RNAs (lncRNAs) can regulate various biological processes in animals and plants. Although lncRNAs have been identified in many plants, they have not been reported in the model plant Nicotiana benthamiana. Particularly, the role of lncRNAs in plant virus infection remains unknown. In this study, we identified lncRNAs in N. benthamiana response to Chinese wheat mosaic virus (CWMV) infection by RNA sequencing. A total of 1175 lncRNAs, including 65 differentially expressed lncRNAs, were identified during CWMV infection. We then analyzed the functions of some of these differentially expressed lncRNAs. Interestingly, one differentially expressed lncRNA, XLOC_006393, was found to participate in CWMV infection as a precursor to microRNAs in N. benthamiana. These results suggest that lncRNAs play an important role in the regulatory network of N. benthamiana in response to CWMV infection.

Download Full-text

A genome-wide screen for differentially methylated long noncoding RNAs identified that lncAC007255.8 is regulated by promoter DNA methylation in Beas-2B cells malignantly transformed by NNK

Toxicology Letters ◽

10.1016/j.toxlet.2021.04.013 ◽

2021 ◽

Author(s):

Enzhao Chen ◽

Jiaxin Zhou ◽

Enwu Xu ◽

Cheng Zhang ◽

Jiayu Liu ◽

...

Keyword(s):

Dna Methylation ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Genome Wide ◽

A Genome ◽

Promoter Dna Methylation ◽

Promoter Dna

Download Full-text

Aberrant expression of long noncoding RNAs in colorectal cancer with liver metastasis

Tumor Biology ◽

10.1007/s13277-015-3627-4 ◽

2015 ◽

Vol 36 (11) ◽

pp. 8747-8754 ◽

Cited By ~ 18

Author(s):

Le-chi Ye ◽

Li Ren ◽

Jun-jun Qiu ◽

De-xiang Zhu ◽

Tao Chen ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Aberrant Expression

Download Full-text

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3072 ◽

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

Download Full-text