Identification of Differentially Expressed Long Noncoding RNAs as Functional Biomarkers and Construction of Function Enrichment Network in Oral Squamous Cell Carcinoma.
Ontology highlight
ABSTRACT: Objective
This study aims to find the novel lncRNAs closely related to the progression of oral squamous cell carcinoma (OSCC) by comprehensively analyzing microarray.Methods
Chip dataset GSE84805 was downloaded from the Gene Expression Omnibus (GEO) database, lncRNA expression profiles of OSCC and paracancerous tissue were obtained, probes sequences reannotation was conducted, and differentially expressed lncRNAs (DELs) and differentially expressed genes (DEGs) were identified. Finally, these data were analyzed by constructing the lncRNA-function enrichment network.Results
We found that 465 lncRNAs are differentially expressed consisting of 193 upregulated lncRNAs and 272 downregulated lncRNAs. Meanwhile, 811 DEGs were identified with 498 upregulated genes and 313 downregulated genes. Analysis of the lncRNA-function enrichment network showed that these aberrant lncRNAs may be related to focal adhesion, inflammatory response pathway, cell cycle, matrix metalloproteinases, and other biological functions. Also, we found that some key lncRNAs such as LINC00152 and HOXA11-AS have been shown to play an important role in tumor proliferation and migration.Conclusion
The key lncRNAs may serve as potential molecular markers or therapeutic targets in OSCC formation and development. It can also help us to understand the molecular mechanism of occurrence and development in OSCC.
SUBMITTER: Xiao F
PROVIDER: S-EPMC9252645 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The most fatal primary brainstem tumors in pediatric patients are diffuse intrinsic pontine gliomas (DIPGs). The identification of genetic alterations, such as the H3K27M mutation, allows a better molecular classification of these tumors. Therefore, the identification of new molecular features, mediating their formation and progression, as non-coding RNAs (ncRNAs), would be of great importance for the development of effective treatments.
2019-10-04 | GSE138402 | GEO
Project description:ObjectiveTo determine the expression profile of small noncoding RNAs (sncRNAs) in leiomyoma, which has not been investigated to date.DesignLaboratory-based investigation.SettingAcademic center.Patient(s)Women undergoing hysterectomy for benign indications.Intervention(s)Next-generation sequencing and screening of an sncRNA database with confirmatory analysis by quantitative reverse-transcription polymerase chain reaction (qRT-PCR).Main outcome measure(s)Expression profile of sncRNAs in leiomyoma and matched myometrium.Result(s)Screening our previously determined RNA sequencing data with the sncRNA database resulted in identification of 15 small nuclear (sn) RNAs, 284 small nucleolar (sno) RNAs, 98 Piwi-interacting (pi) RNAs, 152 transfer (t) RNAs, and 45 ribosomal (r) RNAs, of which 15 snoRNAs, 24 piRNAs, 7 tRNAs, and 6 rRNAs were differentially expressed at a 1.5-fold change cutoff in leiomyoma compared with myometrium. We selected 5 snoRNAs, 4 piRNAs, 1 tRNA, and 1 rRNA that were differentially expressed and confirmed their expression in paired tissues (n = 20) from both phases of the menstrual cycle with the use of qRT-PCR. The results indicated up-regulation of the snoRNAs (SNORD30, SNORD27, SNORA16A, SNORD46, and SNORD56) and down-regulation of the piRNAs (piR-1311, piR-16677, piR-20365, piR-4153), tRNA (TRG-GCC5-1), and rRNA (RNA5SP202) expression in leiomyoma compared with myometrium (P<.05). The pattern of expression of these sncRNAs was similar to RNA sequencing analysis, with no menstrual cycle-dependent differences detected except for SNORD30. Because Argonaute 2 (AGO2) is required for sncRNA-mediated gene silencing, we determined its expression and found greater abundance in leiomyoma.Conclusion(s)Our results provide the first evidence for the differential expression of additional classes of sncRNAs and AGO2 in leiomyoma, implicating their roles as a gene regulatory mechanism.
| S-EPMC6445395 | biostudies-literature
Project description:AimsNoncoding RNAs (ncRNAs) play an important role in the occurrence and development of type 2 diabetes mellitus (T2DM). This paper summarized the current evidences of the involvement microRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in the differential expressions and their interaction with each other in T2DM.MethodsThe differentially expressed miRNAs, lncRNAs, and circRNAs in the blood circulation (plasma, serum, whole blood, and peripheral blood mononuclear cells) of patients with T2DM were found in PubMed, GCBI, and other databases. The interactions between ncRNAs were predicted based on the MiRWalk and the DIANA Tools databases. The indirect and direct target genes of lncRNAs and circRNAs were predicted based on the starBase V2.0, DIANA Tools, and LncRNA-Target databases. Then, GO and KEGG analysis on all miRNA, lncRNA, and circRNA target genes was performed using the mirPath and Cluster Profile software package in R language. The lncRNA-miRNA and circRNA-miRNA interaction diagram was constructed with Cytoscape. The aim of this investigation was to construct a mechanism diagram of lncRNA involved in the regulation of target genes on insulin signaling pathways and AGE-RAGE signaling pathways of diabetic complications.ResultsA total of 317 RNAs, 283 miRNAs, and 20 lncRNAs and circRNAs were found in the circulation of T2DM. Dysregulated microRNAs and lncRNAs were found to be involved in signals related to metabolic disturbances, insulin signaling, and AGE-RAGE signaling in T2DM. In addition, lncRNAs participate in the regulation of key genes in the insulin signaling and AGE-RAGE signaling pathways through microRNAs, which leads to insulin resistance and diabetic vascular complications.ConclusionNoncoding RNAs participate in the occurrence and development of type 2 diabetes and lead to its vascular complications by regulating different signaling pathways.
| S-EPMC7683115 | biostudies-literature
Project description:Retinoblastoma (RB), the most common intraocular malignancy, typically occurs in pediatric patients under the age of 6 years. The present study aimed to explore the long noncoding RNA (lncRNA) expression profile in RB and identify novel lncRNA biomarkers to facilitate the investigation of molecular mechanisms of RB and improve clinical therapy. Raw microarray data for the comparison of gene expression between three RB and three adjacent normal tissue samples were downloaded from Gene Expression Omnibus (dataset no. GSE111168). After identification of differentially expressed lncRNAs (DELs) and differentially expressed mRNAs (DEMs) in RB, functional enrichment analyses and a DEL-DEM weighted correlation network analysis were performed. A total of 3,915 DELs (1,774 upregulated and 2,141 downregulated) and 3,715 DEMs (1,492 upregulated and 2,223 downregulated) were identified in RB. The DEL-targeted DEMs were highly enriched by genes involved in hexose transport, muscle tissue morphogenesis, the stereocilium membrane, endothelin B receptor binding and γ-filamin/ABP-L, α-actinin and telethonin binding protein of the Z-disc binding. Furthermore, associations of the DELs and DEMs with several pathways were determined, including PI3K/AKT, Hippo and cancer signaling, as well as extracellular matrix-receptor interaction pathways. Coexpression network analysis revealed that the top three DELs, lnc-DAZ1-161, lnc-HDAC7-21 and lnc-OR52A1-55, formed coexpression modules with 181, 156 and 210 DEMs, respectively. In addition, the top three DEMs, namely EIF1AY, GSTM1 and NLRP11, formed coexpression modules with 33, 50 and 41 DELs, respectively. Validation using reverse transcription-quantitative PCR indicated that the expression of representative lncRNAs (lnc-DAZ1-161 and lnc-HDAC7-21) in RB cells in vitro was consistent with that in RB tissues in the database, while the expression of lnc-OR52A1-55 was not consistent with the database. These results suggested that the aberrant lncRNA expression profile in RB is related to the differential regulation of numerous physiological and pathological processes. The lncRNA and mRNA profiles in RB identified may provide novel targets for the investigation of its molecular mechanisms and thus lead to improvements in clinical therapy for RB.
| S-EPMC8549103 | biostudies-literature
Project description:Purpose: The purpose of this study was to identify aberrantly expressed lncRNAs, circular RNAs and the associated TF‐mRNA network in TSCC. Methods: Tongue tumor noncoding and mRNA profiles of tongue squamous cell carcinoma and adjacent noncancerous tissues were generated by deep sequencing, using Illumina HiSeq 4000. Results: Using an optimized data analysis workflow. Conclusions: we found a profile of dysregulated lncRNAs, TFs and mRNAs that could serve as prospective clinical biomarkers because of their tissue specificity and association with the tumorigenesis and progression of TSCC.
2020-08-04 | GSE149008 | GEO
Project description:"Pancreatic ductal adenocarcinoma (PDAC) is known by its aggressiveness and lack of effective therapeutic options. Thus, improvement in current knowledge of molecular changes associated with pancreatic cancer is urgently needed to explore novel venues of diagnostics and treatment of this dismal disease. While there is mounting evidence that long noncoding RNAs (ncRNAs) transcribed from intronic and intergenic regions of the human genome may play different roles in the regulation of gene expression in normal and cancer cells, their expression pattern and biological relevance in pancreatic cancer is currently unknown. In the present work we investigated the relative abundance of a collection of ncRNAs in patients’ pancreatic tissue samples aiming at identifying gene expression profiles correlated to pancreatic cancer and metastasis. To investigate the relative abundance, we used a custom 3,355-element spotted cDNA microarray interrogating protein-coding genes and putative ncRNA were used to obtain expression profiles from 38 clinical samples of tumor and non-tumor pancreatic tissues. Bioinformatics analyses were performed to characterize structure and conservation of ncRNAs expressed in pancreatic tissues, as well as to identify expression signatures correlated to tissue histology. Strand-specific reverse transcription followed by PCR and qRT-PCR were employed to determine strandedness of ncRNAs and to validate microarray results, respectively. We found that long intronic/intergenic ncRNAs are ubiquitously expressed across tumor and non-tumor pancreatic tissue samples. Enrichment of promoter-H3K4me3 associated chromatin marks and over-representation of conserved DNA elements and stable secondary structure predictions suggest that these transcripts are generated from independent transcriptional units and that at least a fraction is under evolutionary selection, and thus potentially functional. Statistically significant expression signatures comprising protein-coding mRNAs and long ncRNAs that correlate to PDAC or to pancreatic cancer metastasis were identified. Interestingly, loci harboring intronic ncRNAs differentially expressed in PDAC metastases were enriched in genes associated to the MAPK pathway. Orientation-specific RT-PCR documented that intronic transcripts are expressed in sense, antisense or both orientations relative to protein-coding mRNAs. Differential expression of a subset of intronic ncRNAs (PPP3CB, MAP3K14 and DAPK1 loci) in metastatic samples was confirmed by Real-Time PCR. All this results reveal sets of long intronic ncRNAs expressed in pancreatic tissues whose abundance is correlated to PDAC or metastasis, thus pointing to the potential relevance of this class of transcripts in biological processes related to malignant transformation and metastasis in pancreatic cancer. Fluorescent labeled cDNA targets derived from pancreatic tumor and non-tumor tissue from each patient were combined and hybridized to spotted cDNA microarrays. For each patient, a replicate hybridization was performed. For each sample, there are 4 replicate measurements for each probe. "
| S-ECPF-GEOD-30134 | biostudies-other
Project description:BackgroundSepsis is the primary cause of mortality in the intensive care unit (ICU), mainly due to sepsis-induced dysfunction of essential organs such as the heart and lungs. This study investigated the myocardium's epigenetic characterization from septic mice to identify potential treatment targets for septic myocardial dysfunction.MethodsCecal ligation and puncture (CLP) was used to induce sepsis in male C57BL/6 mice. Hearts were collected 24 h after surgery to determine the expression profiles of long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) by microarray. To validate the reliability of microarray results, we randomly chose six differentially expressed lncRNAs for qRT-PCR. Functional mapping of differentially expressed mRNAs was annotated with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses; lncRNA-mRNA co-expression network was constructed to reveal connections between lncRNAs and mRNAs.ResultsMicroarray analysis indicated that 1,568 lncRNAs and 2,166 mRNAs were differentially expressed in the myocardium from septic mice, which was further confirmed by qRT-PCR. KEGG pathway analysis showed that numerous differentially expressed mRNAs were relevant to tumor necrosis factor (TNF) and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathways. Moreover, according to the lncRNA-mRNA co-expression network constructed by the above six lncRNAs and their interacting mRNAs, the co-expression network profiles had 57 network nodes and 134 connections, including 76 positive interactions and 58 negative interactions.ConclusionsIn mouse hearts, sepsis resulted in differential expression of lncRNAs and mRNAs related to TNF and PI3K-Akt signaling pathways, suggesting that lncRNAs and their interacting mRNAs may participate in the pathogenesis of septic myocardial dysfunction by regulating TNF and PI3K-Akt signaling pathways.
| S-EPMC7940873 | biostudies-literature
Project description:Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide. Metastasis is the main cause of the death of OSCC patients. Long noncoding RNAs (lncRNAs), one of the key factors affecting OSCC metastasis, are a subtype of RNA with a length of more than 200 nucleotides that has little or no coding potential. In recent years, the important role played by lncRNAs in biological processes, such as chromatin modification, transcription regulation, RNA stability regulation, and mRNA translation, has been gradually revealed. More and more studies have shown that lncRNAs can regulate the metastasis of various tumors including OSCC at epigenetic, transcriptional, and post-transcriptional levels. In this review, we mainly discussed the role and possible mechanisms of lncRNAs in OSCC metastasis. Most lncRNAs act as oncogenes and only a few lncRNAs have been shown to inhibit OSCC metastasis. Besides, we briefly introduced the research status of cancer-associated fibroblasts-related lncRNAs in OSCC metastasis. Finally, we discussed the research prospects of lncRNAs-mediated crosstalk between OSCC cells and the tumor microenvironment in OSCC metastasis, especially the potential research value of exosomes and lymphangiogenesis. In general, lncRNAs are expected to be used for screening, treatment, and prognosis monitoring of OSCC metastasis, but more work is still required to better understand the biological function of lncRNAs.
| S-EPMC7845733 | biostudies-literature
Project description:Objectives:This study aims to determine differentially expressed genes (DEGs) and long noncoding RNAs (lncRNAs) associated with Parkinson's disease (PD) using a microarray. Methods:We downloaded the microarray data GSE6613 from the Gene Expression Omnibus, which included 105 samples. We selected 72 samples comprising 22 healthy control blood samples and 50 PD blood samples for further analysis. Later, we used Limma to screen DEGs and differentially expressed lncRNAs (DElncRNAs) and estimated their functions by the Gene Ontology (GO). Besides, the competing endogenous RNA (ceRNA) network, including microRNAs, lncRNAs, and mRNAs, was constructed to elucidate the regulatory mechanism. Furthermore, we performed the KEGG pathway enrichment with mRNAs in the ceRNA regulatory network and constructed a final network, including pathways, mRNAs, microRNAs, and lncRNAs. Results:Overall, we obtained 394 DEGs, including 207 upregulated DEGs and 187 downregulated DEGs, and 7 DElncRNAs, including 2 upregulated DElncRNAs and 5 downregulated DElncRNAs. Insulin-like growth factor-1 receptor (IGF1R) was considerably enriched in the endocytosis pathway. In the ceRNA regulation network, IGF1R was the target of hsa-miR-133b and lncRNAs of XIST, and PART1 could also be the target of hsa-miR-133b. While the upregulated DEGs were enriched in the GO terms of the cytoskeleton, cytoskeletal part, and microtubule cytoskeleton, the downregulated DEGs were enriched in the immune response. PRKACA was markedly enriched in numerous pathways, including the MAPK and insulin signaling pathways. Conclusions:IGF1R, PRKACA, and lncRNA-XIST could be potentially involved in PD, and these diverse molecular mechanisms could support the development of the similar treatment for PD.
| S-EPMC6379850 | biostudies-literature
Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) is known by its aggressiveness and lack of effective therapeutic options. Thus, improvement in current knowledge of molecular changes associated with pancreatic cancer is urgently needed to explore novel venues of diagnostics and treatment of this dismal disease. While there is mounting evidence that long noncoding RNAs (lncRNAs) transcribed from intronic and intergenic regions of the human genome may play different roles in the regulation of gene expression in normal and cancer cells, their expression pattern and biological relevance in pancreatic cancer is currently unknown. In the present work we investigated the relative abundance of a collection of lncRNAs in patients' pancreatic tissue samples aiming at identifying gene expression profiles correlated to pancreatic cancer and metastasis.MethodsCustom 3,355-element spotted cDNA microarray interrogating protein-coding genes and putative lncRNA were used to obtain expression profiles from 38 clinical samples of tumor and non-tumor pancreatic tissues. Bioinformatics analyses were performed to characterize structure and conservation of lncRNAs expressed in pancreatic tissues, as well as to identify expression signatures correlated to tissue histology. Strand-specific reverse transcription followed by PCR and qRT-PCR were employed to determine strandedness of lncRNAs and to validate microarray results, respectively.ResultsWe show that subsets of intronic/intergenic lncRNAs are expressed across tumor and non-tumor pancreatic tissue samples. Enrichment of promoter-associated chromatin marks and over-representation of conserved DNA elements and stable secondary structure predictions suggest that these transcripts are generated from independent transcriptional units and that at least a fraction is under evolutionary selection, and thus potentially functional.Statistically significant expression signatures comprising protein-coding mRNAs and lncRNAs that correlate to PDAC or to pancreatic cancer metastasis were identified. Interestingly, loci harboring intronic lncRNAs differentially expressed in PDAC metastases were enriched in genes associated to the MAPK pathway. Orientation-specific RT-PCR documented that intronic transcripts are expressed in sense, antisense or both orientations relative to protein-coding mRNAs. Differential expression of a subset of intronic lncRNAs (PPP3CB, MAP3K14 and DAPK1 loci) in metastatic samples was confirmed by Real-Time PCR.ConclusionOur findings reveal sets of intronic lncRNAs expressed in pancreatic tissues whose abundance is correlated to PDAC or metastasis, thus pointing to the potential relevance of this class of transcripts in biological processes related to malignant transformation and metastasis in pancreatic cancer.
| S-EPMC3225313 | biostudies-literature