Characterization of long non-coding RNA and messenger RNA profiles in laryngeal cancer by weighted gene co-expression network analysis

Abstract Background Microglia are resident immunocompetent and phagocytic cells in the CNS. Pro-inflammatory microglia, stimulated by microbial signals such as bacterial lipopolysaccharide (LPS), viral RNAs, or inflammatory cytokines, are neurotoxic and associated with pathogenesis of several neurodegenerative diseases. Long non-coding RNAs (lncRNA) are emerging as important tissue-specific regulatory molecules directing cell differentiation and functional states and may help direct proinflammatory responses of microglia. Characterization of lncRNAs upregulated in proinflammatory microglia, such as NR_126553 or 2500002B13Rik, now termed Nostrill (iNOS Transcriptional Regulatory Intergenic LncRNA Locus) increases our understanding of molecular mechanisms in CNS innate immunity. Methods Microglial gene expression array analyses and qRT-PCR were used to identify a novel long intergenic non-coding RNA, Nostrill, upregulated in LPS-stimulated microglial cell lines, LPS-stimulated primary microglia, and LPS-injected mouse cortical tissue. Silencing and overexpression studies, RNA immunoprecipitation, chromatin immunoprecipitation, chromatin isolation by RNA purification assays, and qRT-PCR were used to study the function of this long non-coding RNA in microglia. In vitro assays were used to examine the effects of silencing the novel long non-coding RNA in LPS-stimulated microglia on neurotoxicity. Results We report here characterization of intergenic lncRNA, NR_126553, or 2500002B13Rik now termed Nostrill (iNOS Transcriptional Regulatory Intergenic LncRNA Locus). Nostrill is induced by LPS stimulation in BV2 cells, primary murine microglia, and in cortical tissue of LPS-injected mice. Induction of Nostrill is NF-κB dependent and silencing of Nostrill decreased inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in BV2 and primary microglial cells. Overexpression of Nostrill increased iNOS expression and NO production. RNA immunoprecipitation assays demonstrated that Nostrill is physically associated with NF-κB subunit p65 following LPS stimulation. Silencing of Nostrill significantly reduced NF-κB p65 and RNA polymerase II recruitment to the iNOS promoter and decreased H3K4me3 activating histone modifications at iNOS gene loci. In vitro studies demonstrated that silencing of Nostrill in microglia reduced LPS-stimulated microglial neurotoxicity. Conclusions Our data indicate a new regulatory role of the NF-κB-induced Nostrill and suggest that Nostrill acts as a co-activator of transcription of iNOS resulting in the production of nitric oxide by microglia through modulation of epigenetic chromatin remodeling. Nostrill may be a target for reducing the neurotoxicity associated with iNOS-mediated inflammatory processes in microglia during neurodegeneration.

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Integrative Analysis of lncRNAs, miRNAs, and mRNA-Associated ceRNA Network in an Atopic Dermatitis Recurrence Model

International Journal of Molecular Sciences ◽

10.3390/ijms19103263 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3263 ◽

Cited By ~ 4

Author(s):

Xiaoyu Wang ◽

Kaifan Bao ◽

Peng Wu ◽

Xi Yu ◽

Can Wang ◽

...

Keyword(s):

Atopic Dermatitis ◽

Messenger Rna ◽

Integrative Analysis ◽

Ample Evidence ◽

Cerna Network ◽

Non Coding Rna ◽

Recurrence Model ◽

Non Coding Rnas ◽

Remission Phase ◽

Long Non Coding Rna

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by its chronic nature and relapse. Ample evidence suggests that non-coding RNAs play a major role in AD pathogenesis. However, the mechanism remains unknown, particularly in AD recurrence. Dynamic morphological and cytokine changes were measured throughout the whole course of an FITC-induced AD recurrence murine model. Microarray assay and integrative analysis were performed to comprehensively explore long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) networks. Our results showed that an AD recurrence model was established. Overall, 5766 lncRNAs, 4025 mRNAs, and 202 miRNAs changed after elicitation, whereas, 419 lncRNAs, 349 mRNAs, and more notably, only 23 miRNAs, were dysregulated in the remission phase. Gene ontology (GO) and KEGG pathway enrichment analyses were used to investigate the potential functions of the dysregulated genes. The altered regulation of seven miRNAs and seven lncRNAs were validated in different stages of the model. The competing endogenous RNA (ceRNA) network inferred that lncRNA humanlincRNA0490+ could compete for miR-155-5p binding, through which it might affect Pkiα expression. Altogether, our findings have provided a novel perspective on the potential roles of non-coding RNAs in AD, and suggest that specific non-coding RNAs could be new therapeutic targets against AD recurrence.

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Long Non-Coding RNA (lncRNA) in Oral Squamous Cell Carcinoma: Biological Function and Clinical Application

Cancers ◽

10.3390/cancers13235944 ◽

2021 ◽

Vol 13 (23) ◽

pp. 5944

Author(s):

Jianfei Tang ◽

Xiaodan Fang ◽

Juan Chen ◽

Haixia Zhang ◽

Zhangui Tang

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Molecular Mechanisms ◽

Non Coding Rna ◽

Potential Applications ◽

Non Coding Rnas ◽

Long Non Coding Rna

Oral squamous cell carcinoma (OSCC) is a type of malignancy with high mortality, leading to poor prognosis worldwide. However, the molecular mechanisms underlying OSCC carcinogenesis have not been fully understood. Recently, the discovery and characterization of long non-coding RNAs (lncRNAs) have revealed their regulatory importance in OSCC. Abnormal expression of lncRNAs has been broadly implicated in the initiation and progress of tumors. In this review, we summarize the functions and molecular mechanisms regarding these lncRNAs in OSCC. In addition, we highlight the crosstalk between lncRNA and tumor microenvironment (TME), and discuss the potential applications of lncRNAs as diagnostic and prognostic tools and therapeutic targets in OSCC. Notably, we also discuss lncRNA-targeted therapeutic techniques including CRISPR-Cas9 as well as immune checkpoint therapies to target lncRNA and the PD-1/PD-L1 axis. Therefore, this review presents the future perspectives of lncRNAs in OSCC therapy, but more research is needed to allow the applications of these findings to the clinic.

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LINC01018 and SMIM25 sponged miR-182-5p in endometriosis revealed by the ceRNA network construction

International Journal of Immunopathology and Pharmacology ◽

10.1177/2058738420976309 ◽

2020 ◽

Vol 34 ◽

pp. 205873842097630

Author(s):

Li Jiang ◽

Mengmeng Zhang ◽

Sixue Wang ◽

Yuzhen Xiao ◽

Jingni Wu ◽

...

Keyword(s):

Messenger Rna ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Protein Protein Interaction ◽

Cerna Network ◽

Non Coding Rna ◽

Differentially Expressed Mirnas ◽

Long Non Coding Rna

The current study intended to explore the interaction of the long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) under the background of competitive endogenous RNA (ceRNA) network in endometriosis (EMs). The differentially expressed miRNAs (DEmiRs), differentially expressed lncRNA (DELs), and differentially expressed genes (DEGs) between EMs ectopic (EC) and eutopic (EU) endometrium based on three RNA-sequencing datasets (GSE105765, GSE121406, and GSE105764) were identified, which were used for the construction of ceRNA network. Then, DEGs in the ceRNA network were performed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analysis. Besides, the DEmiRs in the ceRNA network were validated in GSE124010. And the target DELs and DEGs of verified DEmiRs were validated in GSE86534. The correlation of verified DEmiRs, DEGs, and DELs was explored. Moreover, gene set enrichment analysis (GSEA) was applied to investigate the function of verified DEmiRs, DEGs, and DELs. Overall, 1352 DEGs and 595 DELs from GSE105764, along with 27 overlapped DEmiRs between GSE105765 and GSE121406, were obtained. Subsequently, a ceRNA network, including 11 upregulated and 16 downregulated DEmiRs, 7 upregulated and 13 downregulated DELs, 48 upregulated and 46 downregulated DEGs, was constructed. The GO and KEGG pathway analysis showed that this ceRNA network probably was associated with inflammation-related pathways. Furthermore, hsa-miR-182-5p and its target DELs (LINC01018 and SMIM25) and DEGs (BNC2, CHL1, HMCN1, PRDM16) were successfully verified in the validation analysis. Besides, hsa-miR-182-5p was significantly negatively correlated with these target DELs and DEGs. The GSEA analysis implied that high expression of LINC01018, SMIM25, and CHL1, and low expression of hsa-miR-182-5p would activate inflammation-related pathways in endometriosis EU samples. LINC01018 and SMIM25 might sponge hsa-miR-182-5p to upregulate downstream genes such as CHL1 to promote the development of endometriosis.

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