Identifying prognostic lncRNAs based on a ceRNA regulatory network in laryngeal squamous cell carcinoma

Abstract Purpose Growing evidence demonstrates that long non-coding RNAs (lncRNAs) play a crucial role as competing endogenous RNAs (ceRNAs) in tumor occurrence. The lncRNAs’ functions and clinical significance in laryngeal squamous cell carcinoma (LSCC) remain unclear. The study aims to reveal the lncRNA-associated ceRNA regulatory network of LSCC and clarify its clinical relevance. Methods Here, we obtained LSCC transcriptome data from The Cancer Genome Atlas (TCGA) database and identified the differential expression profile of lncRNAs, miRNAs, and mRNAs by the EdgeR R package. The function enrichment analysis of mRNAs was performed using clusterProfiler R package and GSEA3.0. Then, we constructed a ceRNA network and prognosis model based on lncRNAs through bioinformatic methods. Moreover, we explored the functions of prognosis-related lncRNA in LSCC by CCK-8 and transwell assay. Results 1961 lncRNAs, 69 miRNAs, and 2224 mRNAs were identified as differentially expressed genes in LSCC tissues. According to the transcriptome differential expression profile, a ceRNA network containing 61 lncRNAs, 21 miRNAs, and 77 mRNAs was established. Then, four lncRNAs (AC011933.2, FAM30A, LINC02086, LINC02575) were identified from the ceRNA network to build a prognosis model for LSCC patients. And we found that LINC02086 and LINC02575 promoted the proliferation, migration, and invasion of LSCC cells while AC011933.2 and FAM30A inhibited these biological functions in vitro. Furthermore, we validated that LINc02086/miR-770-5p/SLC26A2 axis promoted migration in LSCC. Conclusion Four lncRNAs of the ceRNA network were abnormally expressed and related to patient prognosis in LSCC. They played a significant role in the progress of LSCC via affecting the proliferation and metastasis of tumor cells.

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Identifying Prognostic Lncrnas Based on A ceRNA Regulatory Network in Laryngeal Squamous Cell Carcinoma

10.21203/rs.3.rs-147155/v1 ◽

2021 ◽

Author(s):

Yong Shi ◽

Dongli Yang ◽

Yixiao Qin

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Differential Expression ◽

Squamous Cell ◽

Regulatory Network ◽

Laryngeal Squamous Cell Carcinoma ◽

R Package ◽

Cerna Network ◽

Prognosis Model ◽

Differential Expression Profile

Abstract Purpose Growing evidence demonstrates that long non-coding RNAs (lncRNAs) play a crucial role as competing endogenous RNAs (ceRNAs) in tumor occurrence. The lncRNAs' function and clinical significance in laryngeal squamous cell carcinoma (LSCC) remain unclear. The study aims to reveal the lncRNA-associated ceRNA regulatory network in LSCC and clarify its clinical relevance.Methods Here, we obtained LSCC transcriptome sequencing data from The Cancer Genome Atlas (TCGA) database and identified the differential expression profile of lncRNAs, miRNAs, and mRNAs by the EdgeR R package. The function enrichment analysis of mRNAs was performed using clusterProfiler R package and GSEA3.0. Then, we constructed a ceRNA network and a prognosis model based on lncRNAs through bioinformatic methods. Moreover, we explored the functions of prognosis-related lncRNA in LSCC by CCK-8 and transwell assay. Results 1961 lncRNAs, 69 miRNAs, and 2224 mRNAs were identified as differentially expressed genes in LSCC tissues. According to the transcriptome differential expression profile, a ceRNA network containing 61 lncRNAs, 21 miRNAs, and 77 mRNAs was established. Then, four lncRNAs (AC011933.2, FAM30A, LINC02086, LINC02575) were extracted from the ceRNA network to build a prognosis model for LSCC patients. Furthermore, we found that LINC02086 and LINC02575 promoted the proliferation, migration, and invasion of LSCC cells while AC011933.2 and FAM30A inhibited these biological functions in vitro. Conclusion Four lncRNAs from the ceRNA network were abnormally expressed and related to patient prognosis in LSCC. They played a significant role in the progress of LSCC via affecting the proliferation and metastasis of tumor cells.

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Comprehensive analysis of differentially expressed profiles of lncRNAs, mRNAs, and miRNAs in laryngeal squamous cell carcinoma in order to construct a ceRNA network and identify potential biomarkers

Journal of Cellular Biochemistry ◽

10.1002/jcb.29063 ◽

2019 ◽

Vol 120 (10) ◽

pp. 17963-17974 ◽

Cited By ~ 5

Author(s):

Xinru Kong ◽

Jixia Qi ◽

Yao Yan ◽

Liwei Chen ◽

Yali Zhao ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Comprehensive Analysis ◽

Differentially Expressed ◽

Cerna Network ◽

Potential Biomarkers

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72P Differential expression profile of lung squamous cell carcinoma (LSCC) cell lines as a mean to predict drug interaction effects

Journal of Thoracic Oncology ◽

10.1016/s1556-0864(16)30185-x ◽

2016 ◽

Vol 11 (4) ◽

pp. S85-S86 ◽

Cited By ~ 1

Author(s):

A. Verlicchi ◽

N. Karachaliou ◽

C. Lazzari ◽

C. Codony Servat ◽

I. Chaib ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Drug Interaction ◽

Cell Carcinoma ◽

Differential Expression ◽

Cell Lines ◽

Expression Profile ◽

Squamous Cell ◽

Lung Squamous Cell Carcinoma ◽

Interaction Effects ◽

Differential Expression Profile

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LncRNA-Associated ceRNA Network Reveals Novel Potential Biomarkers of Laryngeal Squamous Cell Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033820985787 ◽

2020 ◽

Vol 19 ◽

pp. 153303382098578

Author(s):

Zhibin Jing ◽

Sitong Guo ◽

Peng Zhang ◽

Zheng Liang

Keyword(s):

Functional Analysis ◽

Squamous Cell Carcinoma ◽

Survival Analysis ◽

Cell Carcinoma ◽

Squamous Cell ◽

Prognostic Value ◽

Laryngeal Squamous Cell Carcinoma ◽

Expression Profiles ◽

The Cancer Genome Atlas ◽

Cerna Network

Objective: This study aims to construct a systematic mRNA-miRNA-lncRNA network to identify novel lncRNAs and miRNAs biomarkers for laryngeal squamous cell carcinoma (LSCC). Methods: The mRNA, miRNA and lncRNA expression profiles of LSCC were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs, miRNAs and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) were screened between LSCC tissues and controls. Functional analysis of DEmRNAs, DEmRNAs targeted by DEmiRNAs and DEmRNAs targeted by DElncRNAs were respectively performed. The miRWalk, starbase and DIANA-LncBase were respectively used to predict DEmiRNAs-DEmRNAs, DElncRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. ceRNA network was built by DEmiRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. LncRNA subcellular localization was predicted using lncLocator. Using published The Cancer Genome Atlas (TCGA) and external datasets (GSE127165 and GSE133632), we also validated the expression of key DElncRNAs and DEmiRNAs in ceRNA network. The diagnostic and prognostic value of candidate genes was evaluated by ROC curve analysis and survival analysis, respectively. Results: There were 5 mRNA datasets, 3 miRNA datasets and 2 lncRNA datasets in this study. Totally, 2957 DEmRNAs, 61 DElncRNAs and 23 DEmiRNAs were identified. Functional analysis of DEmRNAs shows that they were significantly enriched in cancer-related pathways, such as DNA replication and extracellular matrix organization. There were 11 DEmiRNAs, 17 DElncRNAs and 967 DEmRNAs in the ceRNA network. Notably, up-regulated lncRNA DGCR5-down-regulated has-miR-338-3p/has-miR-139-5p pairs in this network were experimentally validated. Moreover, down-regulated AL121839.2, down-regulated LINC02147, up-regulated AC079328.2, up-regulated AC004943.2 and up-regulated HMGA2-AS1 were located in the cytoplasm. AL121839.2 and LINC02147 interacted with has-miR-1246. AC004943.2, AC079328.2 and HMGA2-AS1 targeted has-miR-3185, has-miR-3137 and has-miR-582-5p, respectively. Based on the TCGA and external datasets (GSE127165 and GSE133632), DGCR5 and AC004943.2 were significantly up-regulated while AL121839.2 and LINC02147, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p were significantly down-regulated, which were consistent with our integration analysis. DGCR5, AL121839.2, LINC02147, AC004943.2, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p could predict the occurrence of LSCC. Survival analysis suggested that only, AL121839.2 has potential prognostic value for LSCC. Conclusion: This study provided novel insights into the ceRNA network and uncovered novel lncRNAs and miRNAs with diagnostic value in LSCC.

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lncRNA TMEM51-AS1 and RUSC1-AS1 function as ceRNAs for induction of laryngeal squamous cell carcinoma and prediction of prognosis

PeerJ ◽

10.7717/peerj.7456 ◽

2019 ◽

Vol 7 ◽

pp. e7456 ◽

Cited By ~ 3

Author(s):

Lian Hui ◽

Jing Wang ◽

Jialiang Zhang ◽

Jin Long

Keyword(s):

Squamous Cell Carcinoma ◽

Regression Analysis ◽

Cell Carcinoma ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Cox Regression ◽

Negative Relationship ◽

Prognostic Biomarkers ◽

Cox Regression Analysis ◽

Cerna Network

Background Long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) to interact with miRNAs to regulate target genes and promote cancer initiation and progression. The expression of lncRNAs and miRNAs can be epigenetically regulated. The goal of this study was to construct an lncRNA-miRNA-mRNA ceRNA network in laryngeal squamous cell carcinoma (LSCC) and reveal their methylation patterns, which was not investigated previously. Methods Microarray datasets available from the Gene Expression Omnibus database were used to identify differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) between LSCC and controls, which were then overlapped with differentially methylated regions (DMRs). The ceRNA network was established by screening the interaction relationships between miRNAs and lncRNAs/mRNAs by corresponding databases. TCGA database was used to identify prognostic biomarkers. Results Five DELs (downregulated: TMEM51-AS1, SND1-IT1; upregulated: HCP5, RUSC1-AS1, LINC00324) and no DEMs were overlapped with the DMRs, but only a negative relationship occurred in the expression and methylation level of TMEM51-AS1. Five DELs could interact with 11 DEMs to regulate 242 DEGs, which was used to construct the ceRNA network, including TMEM51-AS1-miR-106b-SNX21/ TRAPPC10, LINC00324/RUSC1-AS1-miR-16-SPRY4/MICAL2/ SLC39A14, RUSC1-AS1-miR-10-SCG5 and RUSC1-AS1-miR-7-ZFP1 ceRNAs axes. Univariate Cox regression analysis showed RUSC1-AS1 and SNX21 were associated with overall survival (OS); LINC00324, miR-7 and ZFP1 correlated with recurrence-free survival (RFS); miR-16, miR-10, SCG5, SPRY4, MICAL2 and SLC39A14 were both OS and RFS-related. Furthermore, TRAPPC10 and SLC39A14 were identified as independent OS prognostic factors by multivariate Cox regression analysis. Conclusion DNA methylation-mediated TMEM51-AS1 and non-methylation-mediated RUSC1-AS1 may function as ceRNAs for induction of LSCC. They and their ceRNA axis genes (particularly TMEM51-AS1-miR-106b-TRAPPC10; RUSC1-AS1-miR-16-SLC39A14) may be potentially important prognostic biomarkers for LSCC.

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Whole-Transcriptome Analysis of CD133+CD144+ Cancer Stem Cells Derived from Human Laryngeal Squamous Cell Carcinoma Cells

Cellular Physiology and Biochemistry ◽

10.1159/000490992 ◽

2018 ◽

Vol 47 (4) ◽

pp. 1696-1710 ◽

Cited By ~ 19

Author(s):

Yongyan Wu ◽

Yuliang Zhang ◽

Min Niu ◽

Yong Shi ◽

Hongliang Liu ◽

...

Keyword(s):

Stem Cells ◽

Squamous Cell Carcinoma ◽

Cancer Stem Cells ◽

Cell Carcinoma ◽

Laryngeal Cancer ◽

Squamous Cell ◽

Regulatory Network ◽

Laryngeal Squamous Cell Carcinoma ◽

Differentially Expressed ◽

Luciferase Reporter

Background/Aims: CD133+CD44+ cancer stem cells previously isolated from laryngeal squamous cell carcinoma (LSCC) cell lines showed strong malignancy and tumorigenicity. However, the molecular mechanism underlying the enhanced malignancy remained unclear. Methods: Cell proliferation assay, spheroid-formation experiment, RNA sequencing (RNA-seq), miRNA-seq, bioinformatic analysis, quantitative real-time PCR, migration assay, invasion assay, and luciferase reporter assay were used to identify differentially expressed mRNAs, lncRNAs, circRNAs and miRNAs, construct transcription regulatory network, and investigate functional roles and mechanism of circRNA in CD133+CD44+ laryngeal cancer stem cells. Results: Differentially expressed genes in TDP cells were mainly enriched in the biological processes of cell differentiation, regulation of autophagy, negative regulation of cell death, regulation of cell growth, response to hypoxia, telomere maintenance, cellular response to gamma radiation, and regulation of apoptotic signaling, which are closely related to the malignant features of tumor cells. We constructed the regulatory network of differentially expressed circRNAs, miRNAs and mRNAs. qPCR findings for the expression of key genes in the network were consistent with the sequencing data. Moreover, our data revealed that circRNA hg19_circ_0005033 promotes proliferation, migration, invasion, and chemotherapy resistance of laryngeal cancer stem cells. Conclusions: This study provides potential biomarkers and targets for LSCC diagnosis and therapy, and provide important evidences for the heterogeneity of LSCC cells at the transcription level.

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Construction and integrated analysis of crosstalking ceRNAs networks in laryngeal squamous cell carcinoma

PeerJ ◽

10.7717/peerj.7380 ◽

2019 ◽

Vol 7 ◽

pp. e7380 ◽

Cited By ~ 5

Author(s):

Yuehui Liu ◽

Fan Ye

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Expression Profiles ◽

Therapeutic Targets ◽

Regulatory Function ◽

Integrated Analysis ◽

Cerna Network ◽

Wide Range

Background Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumours of the head and neck. Recent evidence has demonstrated that lncRNAs play important roles in tumour progression and could be used as biomarkers for early diagnosis, prognosis, and potential therapeutic targets. The “competitive endogenous RNA (ceRNA)” hypothesis states that lncRNAs competitively bind to miRNAs through their intramolecular miRNA reaction elements (MREs) to construct a wide range of ceRNA regulatory networks. This study aims to predict the role of ceRNA network in LSCC, for advancing the understanding of underlying mechanisms of tumorigenesis. Material and Methods In this study, the functions of lncRNAs as ceRNAs in LSCC and their prognostic significance were investigated via comprehensive integrated expression profiles data of lncRNAs, mRNAs, and miRNAs obtained from The Cancer Genome Atlas (TCGA). Protein–protein interaction, gene ontology, pathway, and Kaplan–Meier curves analysis were used to profile the expression and function of altered RNAs in LSCC. Results As a result, 889 lncRNAs, 55 miRNAs and 1946 mRNAs were found to be differentially expressed in LSCC. These altered mRNAs were mainly involved in extracellular matrix organization, calcium signaling, and metabolic pathways. To study the regulatory function of lncRNAs, an lncRNA-mediated ceRNA network was constructed. This ceRNA network included 61 lncRNAs, seven miRNAs and seven target mRNAs. Of these RNAs, lncRNAs (TSPEAR-AS, CASK-AS1, MIR137HG, PART1, LSAMP-AS1), miRNA (has-mir-210) and mRNAs (HOXC13, STC2, DIO1, FOXD4L1) had a significant effect on the prognosis of LSCC. Conclusion The results of this study broaden the understanding of the mechanisms by which lncRNAs are involved in tumorigenesis. Furthermore, five lncRNAs (TSPEAR-AS, CASK-AS1, MIR137HG, PART1, LSAMP-AS1) were identified as potential prognostic biomarkers and therapeutic targets for LSCC. These results provide a basis for further experimental and clinical research.

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