scholarly journals Construction and investigation of lncRNA-miRNA-mRNA ceRNA network in thymic epithelial neoplasms

2020 ◽  
Author(s):  
Hanxiao Tang ◽  
Shuyu Ge ◽  
Pingping Sun

Abstract Background Competing endogenous RNA (ceRNA) networks may be used to relate the functions of protein-coding mRNAs with those of the non-coding RNAs, such as microRNAs (miRNAs) and the long non-coding RNAs (lncRNAs). ceRNAs enable the post-transcriptional regulation of gene expression by competing for the shared miRNAs. However, the role and function of the lncRNA-miRNA-mRNA ceRNA network in thymic epithelial neoplasms (TEN) remains unknown. Methods The miRNA, mRNA, and lncRNA expression profiles of 124 patients with TEN were downloaded from The Cancer Genome Atlas. We identified the differentially expressed (DE) miRNAs, mRNAs, and lncRNAs using the limma package in R software. The GDCRNATools package was used for the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations. Cytoscape software was used to construct the lncRNA-miRNA-mRNA ceRNA network. The Gene Expression Profiling Interactive Analysis platform was used to estimate the overall survival (OS) rates of the patients. Survival curves were analyzed using the log-rank test. Finally, the mRNAs in the ceRNA network were analyzed using the GOplot package in R. Results A total of 1513, 188, and 579 TEN-specific mRNAs, lncRNAs, and miRNAs, respectively, were identified. The lncRNA-miRNA-mRNA ceRNA network was constructed, and included 53 mRNAs, 4 lncRNAs, and 27 miRNAs. A total of 10 DEmRNAs (DLX2, C8orf88, CD38, GATA3, MAL, FOXQ1, FOLH1, NLRP12, HJURP, and ACSM1) and 1 lncRNA (SNHG3) were found to be significantly associated with OS ( P <0.05). Conclusion In this study, we constructed a lncRNA-miRNA-mRNA ceRNA gene regulatory network for TEN, and identified potential prognostic and diagnostic biomarkers, as well as therapeutic targets, for the disease.

2010 ◽  
Vol 38 (2) ◽  
pp. 617-621 ◽  
Author(s):  
Robert T. Grant-Downton

The various classes of small non-coding RNAs are a fundamentally important component of the transcriptome. These molecules have roles in many essential processes such as regulation of gene expression at the transcriptional and post-transcriptional levels, guidance of DNA methylation and defence against selfish replicators such as transposons. Their diversity and functions in the sporophytic generation of angiosperms is well explored compared with the gametophytic generation, where little is known about them. Recent progress in understanding their abundance, diversity and function in the gametophyte is reviewed.


2021 ◽  
Author(s):  
Zhuoqi Li ◽  
Jing Zhou ◽  
Liankun Gu ◽  
Baozhen Zhang

Abstract Colorectal cancer (CRC) is one of the most common and deadly malignant carcinomas. Many long noncoding RNAs (lncRNA) have been reported to play an important role in the tumorigenesis of CRC by interacting with miRNAs and influencing the expression of some mRNAs through a competing endogenous RNA (ceRNA) network. Pseudogenes are one kind of lncRNA and can act as RNA sponges for miRNAs and regulate gene expression via ceRNA networks, but there are few studies about pseudogenes in CRC. In this study, total of 31 differentially expressed (DE) pseudogenes, 17 DE miRNAs and 152 DE mRNAs were identified by analyzing the expression profiles of colon adenocarcinoma (COAD) obtained from The Cancer Genome Atlas (TCGA). And a ceRNA network was constructed based on these RNAs. Kaplan–Meier analysis showed that 7 pseudogenes, 4 miRNAs and 30 mRNAs were significantly associated with overall survival. Then multivariate Cox regression analysis on the ceRNA-related DE pseudogenes was performed and a 5-pseudogene signature with the greatest prognostic value for CRC was identified. What’s more, the results were validated by the Gene Expression Omnibus (GEO) database, and quantitative real‐time PCR (qRT‐PCR) in 113 pairs of CRC tissues. In conclusion, this study provides a pseudogene-associated ceRNA network and 7 prognostic pseudogene biomarkers, and a 5-pseudogene prognostic risk signature that may be useful to predict the survival of CRC patients.


2021 ◽  
Vol 6 ◽  
pp. 36
Author(s):  
Michele Tinti ◽  
Anna Kelner-Mirôn ◽  
Lizzie J. Marriott ◽  
Michael A.J. Ferguson

Background: The contrasting physiological environments of Trypanosoma brucei procyclic (insect vector) and bloodstream (mammalian host) forms necessitates deployment of different molecular processes and, therefore, changes in protein expression. Transcriptional regulation is unusual in T. brucei because the arrangement of genes is polycistronic; however, genes which are transcribed together are subsequently cleaved into separate mRNAs by trans-splicing. Following pre-mRNA processing, the regulation of mature mRNA stability is a tightly controlled cellular process. While many stage-specific transcripts have been identified, previous studies using RNA-seq suggest that changes in overall transcript level do not necessarily reflect the abundance of the corresponding protein. Methods: To better understand the regulation of gene expression in T. brucei, we performed a bioinformatic analysis of RNA-seq on total, sub-polysomal, and polysomal mRNA samples. We further cross-referenced our dataset with a previously published proteomics dataset to identify new protein coding sequences. Results: Our analyses showed that several long non-coding RNAs are more abundant in the sub-polysome samples, which possibly implicates them in regulating cellular differentiation in T. brucei. We also improved the annotation of the T.brucei genome by identifying new putative protein coding transcripts that were confirmed by mass spectrometry data. Conclusions: Several long non-coding RNAs are more abundant in the sub-polysome cellular fractions and might pay a role in the regulation of gene expression. We hope that these data will be of wide general interest, as well as being of specific value to researchers studying gene regulation expression and life stage transitions in T. brucei.


2021 ◽  
Author(s):  
Milca Rachel da Costa Ribeiro Lins ◽  
Laura Araujo da Silva Amorim ◽  
Graciely Gomes Correa ◽  
Bruno Willian Picao ◽  
Matthias Mack ◽  
...  

Our growing knowledge of the diversity of non-coding RNAs in natural systems and our deepening knowledge of RNA folding and function have fomented the rational design of RNA regulators. Based on that knowledge, we designed and implemented a small RNA (sRNA) tool to target bacterial riboswitches and activate gene expression. The synthetic sRNA is suitable for the regulation of gene expression both in cell-free and in cellular systems. It targets riboswitches to promote the antitermination folding regardless the cognate metabolite concentration. Therefore, it prevents transcription termination increasing gene expression up to 103-fold. We successfully used sRNA arrays for multiplex targeting of riboswitches. Finally, we used the synthetic sRNA to engineer an improved riboflavin producer strain. The easiness to design and construct, and the fact that the riboswitch-targeting sRNA works as a single genome copy, make it an attractive tool for engineering industrial metabolite-producing strains.


Oncotarget ◽  
2015 ◽  
Vol 6 (22) ◽  
pp. 19070-19086 ◽  
Author(s):  
María Laura Gutiérrez ◽  
Luis Corchete ◽  
Cristina Teodosio ◽  
María Eugenia Sarasquete ◽  
María del Mar Abad ◽  
...  

2013 ◽  
Vol 4 (4) ◽  
pp. 411-415 ◽  
Author(s):  
Nadia Vadaie ◽  
Kevin V. Morris

AbstractShortly after the completion of the human genome project in 2003, the Encode project was launched. The project was set out to identify the functional elements in the human genome, and unexpectedly it was found that >80% of the genome is transcribed. The Encode project identified those transcribed regions of the genome to be encoded by non-coding RNAs (ncRNAs). With only 2% of the genome carrying gene-encoding proteins, the conundrum was then, what is the function, if any, of these non-coding regions of the genome? These ncRNAs included both short and long RNAs. The focus of this review will be on antisense long non-coding RNAs (lncRNAs), as these transcripts have been observed to play a role in gene expression of protein-coding genes. Some lncRNAs have been found to regulate protein-coding gene transcription at the epigenetic level, whereby they suppress transcription through the recruitment of protein complexes to target loci in the genome. Conversely, there are lncRNAs that have a positive role in gene expression with less known about mechanism, and some lncRNAs have been shown to be involved in post-transcriptional processes. Additionally, lncRNAs have been observed to regulate their own expression in a positive feedback loop by functioning as a decoy. The biological significance of lncRNAs is only just now becoming evident, with many lncRNAs found to play a significant role in several human diseases.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Guoliang Jia ◽  
Zheyu Song ◽  
Zhonghang Xu ◽  
Youmao Tao ◽  
Yuanyu Wu ◽  
...  

Abstract Background Bioinformatics was used to analyze the skin cutaneous melanoma (SKCM) gene expression profile to provide a theoretical basis for further studying the mechanism underlying metastatic SKCM and the clinical prognosis. Methods We downloaded the gene expression profiles of 358 metastatic and 102 primary (nonmetastatic) CM samples from The Cancer Genome Atlas (TCGA) database as a training dataset and the GSE65904 dataset from the National Center for Biotechnology Information database as a validation dataset. Differentially expressed genes (DEGs) were screened using the limma package of R3.4.1, and prognosis-related feature DEGs were screened using Logit regression (LR) and survival analyses. We also used the STRING online database, Cytoscape software, and Database for Annotation, Visualization and Integrated Discovery software for protein–protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses based on the screened DEGs. Results Of the 876 DEGs selected, 11 (ZNF750, NLRP6, TGM3, KRTDAP, CAMSAP3, KRT6C, CALML5, SPRR2E, CD3G, RTP5, and FAM83C) were screened using LR analysis. The survival prognosis of nonmetastatic group was better compared to the metastatic group between the TCGA training and validation datasets. The 11 DEGs were involved in 9 KEGG signaling pathways, and of these 11 DEGs, CALML5 was a feature DEG involved in the melanogenesis pathway, 12 targets of which were collected. Conclusion The feature DEGs screened, such as CALML5, are related to the prognosis of metastatic CM according to LR. Our results provide new ideas for exploring the molecular mechanism underlying CM metastasis and finding new diagnostic prognostic markers.


Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1132
Author(s):  
Emel Rothzerg ◽  
Xuan Dung Ho ◽  
Jiake Xu ◽  
David Wood ◽  
Aare Märtson ◽  
...  

The human genome encodes thousands of natural antisense long noncoding RNAs (lncRNAs); they play the essential role in regulation of gene expression at multiple levels, including replication, transcription and translation. Dysregulation of antisense lncRNAs plays indispensable roles in numerous biological progress, such as tumour progression, metastasis and resistance to therapeutic agents. To date, there have been several studies analysing antisense lncRNAs expression profiles in cancer, but not enough to highlight the complexity of the disease. In this study, we investigated the expression patterns of antisense lncRNAs from osteosarcoma and healthy bone samples (24 tumour-16 bone samples) using RNA sequencing. We identified 15 antisense lncRNAs (RUSC1-AS1, TBX2-AS1, PTOV1-AS1, UBE2D3-AS1, ERCC8-AS1, ZMIZ1-AS1, RNF144A-AS1, RDH10-AS1, TRG-AS1, GSN-AS1, HMGA2-AS1, ZNF528-AS1, OTUD6B-AS1, COX10-AS1 and SLC16A1-AS1) that were upregulated in tumour samples compared to bone sample controls. Further, we performed real-time polymerase chain reaction (RT-qPCR) to validate the expressions of the antisense lncRNAs in 8 different osteosarcoma cell lines (SaOS-2, G-292, HOS, U2-OS, 143B, SJSA-1, MG-63, and MNNG/HOS) compared to hFOB (human osteoblast cell line). These differentially expressed IncRNAs can be considered biomarkers and potential therapeutic targets for osteosarcoma.


2021 ◽  
Vol 7 (3) ◽  
pp. 42
Author(s):  
Victoria Mamontova ◽  
Barbara Trifault ◽  
Lea Boten ◽  
Kaspar Burger

Gene expression is an essential process for cellular growth, proliferation, and differentiation. The transcription of protein-coding genes and non-coding loci depends on RNA polymerases. Interestingly, numerous loci encode long non-coding (lnc)RNA transcripts that are transcribed by RNA polymerase II (RNAPII) and fine-tune the RNA metabolism. The nucleolus is a prime example of how different lncRNA species concomitantly regulate gene expression by facilitating the production and processing of ribosomal (r)RNA for ribosome biogenesis. Here, we summarise the current findings on how RNAPII influences nucleolar structure and function. We describe how RNAPII-dependent lncRNA can both promote nucleolar integrity and inhibit ribosomal (r)RNA synthesis by modulating the availability of rRNA synthesis factors in trans. Surprisingly, some lncRNA transcripts can directly originate from nucleolar loci and function in cis. The nucleolar intergenic spacer (IGS), for example, encodes nucleolar transcripts that counteract spurious rRNA synthesis in unperturbed cells. In response to DNA damage, RNAPII-dependent lncRNA originates directly at broken ribosomal (r)DNA loci and is processed into small ncRNA, possibly to modulate DNA repair. Thus, lncRNA-mediated regulation of nucleolar biology occurs by several modes of action and is more direct than anticipated, pointing to an intimate crosstalk of RNA metabolic events.


NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Keisuke Katsushima ◽  
George Jallo ◽  
Charles G Eberhart ◽  
Ranjan J Perera

Abstract Long non-coding RNAs (lncRNAs) have been found to be central players in the epigenetic, transcriptional and post-transcriptional regulation of gene expression. There is an accumulation of evidence on newly discovered lncRNAs, their molecular interactions and their roles in the development and progression of human brain tumors. LncRNAs can have either tumor suppressive or oncogenic functions in different brain cancers, making them attractive therapeutic targets and biomarkers for personalized therapy and precision diagnostics. Here, we summarize the current state of knowledge of the lncRNAs that have been implicated in brain cancer pathogenesis, particularly in gliomas and medulloblastomas. We discuss their epigenetic regulation as well as the prospects of using lncRNAs as diagnostic biomarkers and therapeutic targets in patients with brain tumors.


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