scholarly journals Circular RNA Expression Profile in Laryngeal Squamous Cell Carcinoma Revealed by Microarray

2018 ◽  
Vol 50 (1) ◽  
pp. 342-352 ◽  
Author(s):  
Yue Fan ◽  
Xin Xia ◽  
Yingying Zhu ◽  
Wenwen Diao ◽  
Xiaoli Zhu ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Regulation Of Gene Expression ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Global Changes ◽  
Laryngeal Mucosa

Background/Aims: A growing body of evidence has suggested that circular RNAs (circRNAs) have crucial functions in the regulation of gene expression, and their dysregulation has been implicated in various types of cancers. However, the roles of circRNAs in laryngeal cancer remain largely unknown. This study investigated the global changes in the expression pattern of circRNAs in laryngeal squamous cell carcinoma (LSCC) to identify potential differentially expressed circRNAs. Methods: Microarray-based circRNA expression was determined in LSCC and paired normal laryngeal tissues. Pathway analyses of the genes producing differentially expressed circRNAs were performed to predict the function of circRNAs using standard enrichment computational methods. Expression levels of candidate circRNAs and microRNAs (miRNAs) were detected by quantitative real-time PCR. The circRNA/ miRNA interactions were constructed using bioinformatics methods to predict the binding of miRNA with circRNA. Results: We identified 506 differentially expressed circRNAs from human LSCC and normal laryngeal mucosa tissues. We confirmed that hsa_circ_0044520 and hsa_circ_0044529 were significantly upregulated in LSCC tissues. The most likely potential target miRNAs for hsa_ circ_0044520 and hsa_circ_0044529 were hsa-miR-4726-5p and hsa-miR-4640-5p, respectively. Functional analysis showed that hsa_circ_0044520 and hsa_circ_0044529 were involved in the process of collagen synthesis. Conclusion: Competitive endogenous RNA network prediction and bioinformatics functional analysis revealed that hsa_circ_0044520 and hsa_circ_0044529 play important regulatory roles by sponging hsa-miR-4726-5p and hsa-miR-4640-5p, thereby providing novel insights into the tumorigenesis of LSCC.

scholarly journals Salivary Circular RNAs Hsa_Circ_0001874 and Hsa_Circ_0001971 as Novel Biomarkers for the Diagnosis of Oral Squamous Cell Carcinoma

2018 ◽  
Vol 47 (6) ◽  
pp. 2511-2521 ◽  
Author(s):  
Si-Yu Zhao ◽  
Jun Wang ◽  
Shao-Bo Ouyang ◽  
Zi-Kun Huang ◽  
Lan Liao
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Roc Curve ◽  
Tnm Stage ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Healthy Controls ◽  
Novel Biomarkers

Background/Aims: Recent studies have demonstrated that circular RNAs (circRNAs) can serve as potential molecular markers for disease diagnosis. However, little is known about their diagnostic potential for oral squamous cell carcinoma (OSCC). This study aimed to determine the expression of circRNAs in the saliva of OSCC patients to identify novel biomarkers for OSCC screening. Methods: Microarray screening of circRNA was performed to identify differentially expressed circRNAs in saliva from 3 OSCC patients compared with 3 healthy controls. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the results, and the association between these confirmed salivary circRNAs and clinicopathological features was analyzed using the chi-squared test. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the circRNAs identified. Preoperative expression and postoperative expression (1 month after the surgery) of hsa_circ_0001874 and hsa_circ_0001971 was also determined. Results: Our results indicated 12 upregulated and 20 downregulated circRNAs in the saliva from the OSCC patients compared with that from the healthy controls. Among the differentially expressed circRNAs, hsa_circ_0001874, hsa_circ_0001971, and hsa_circ_0008068 were upregulated and hsa_circ_0000140, hsa_circ_0002632, and hsa_circ_0008792 were downregulated in the OSCC group versus the healthy group. Clinical data indicated that salivary hsa_circ_0001874 was correlated with TNM stage (P=0.006) and tumor grade (P=0.023) and that hsa_circ_0001971 was correlated with TNM stage (P=0.019). The combination of hsa_circ_0001874 and hsa_circ_0001971 showed an area under the ROC curve of 0.922 (95% confidence interval, 0.883-0.961; P< 0.001). The risk score based on the combination of hsa_circ_0001874 and hsa_circ_0001971 also discriminated patients with OSCC from patients with oral leukoplakia (P< 0.001). Moreover, the expression levels of salivary hsa_circ_0001874 and hsa_circ_0001971 were clearly decreased in the postoperative samples compared with preoperative samples (P< 0.001). Conclusions: This is the first study to demonstrate the potential of salivary hsa_circ_0001874 and hsa_circ_0001971 as biomarkers for the diagnosis of OSCC.

scholarly journals circPARD3 drives malignant progression and chemoresistance of laryngeal squamous cell carcinoma by inhibiting autophagy through the PRKCI-Akt-mTOR pathway

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Wei Gao ◽  
Huina Guo ◽  
Min Niu ◽  
Xiwang Zheng ◽  
Yuliang Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Mtor Pathway ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Autophagic Flux ◽  
In Vivo Models ◽  
Potential Biomarker

Abstract Background Laryngeal squamous cell carcinoma (LSCC) is the second most common malignant tumor in head and neck. Autophagy and circular RNAs (circRNAs) play critical roles in cancer progression and chemoresistance. However, the function and mechanism of circRNA in autophagy regulation of LSCC remain unclear. Methods The autophagy-suppressive circRNA circPARD3 was identified via RNA sequencing of 107 LSCC tissues and paired adjacent normal mucosal (ANM) tissues and high-content screening. RT-PCR, Sanger sequencing, qPCR and fluorescence in situ hybridization were performed to detect circPARD3 expression and subcellular localization. Biological functions of circPARD3 were assessed by proliferation, migration, invasion, autophagic flux, and chemoresistance assays using in vitro and in vivo models. The mechanism of circPARD3 was investigated by RNA immunoprecipitation, RNA pulldown, luciferase reporter assays, western blotting and immunohistochemical staining. Results Autophagy was inhibited in LSCC, and circPARD3 was upregulated in the LSCC tissues (n = 100, p < 0.001). High circPARD3 level was associated with advanced T stages (p < 0.05), N stages (p = 0.001), clinical stages (p < 0.001), poor differentiation degree (p = 0.025), and poor prognosis (p = 0.002) of LSCC patients (n = 100). Functionally, circPARD3 inhibited autophagy and promoted LSCC cell proliferation, migration, invasion and chemoresistance. We further revealed that activation of the PRKCI-Akt-mTOR pathway through sponging miR-145-5p was the main mechanism of circPARD3 inhibited autophagy, promoting LSCC progression and chemoresistance. Conclusion Our study reveals that the novel autophagy-suppressive circPARD3 promotes LSCC progression and chemoresistance through the PRKCI-Akt-mTOR pathway, providing new insights into circRNA-mediated autophagy regulation and potential biomarker and target for LSCC treatment. Graphical abstract

scholarly journals A Novel Signature Derived from Metabolism-Related Genes GPT and SMS to Predict Prognosis of Laryngeal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Yujie Shen ◽  
Qiang Huang ◽  
Yifan Zhang ◽  
Chi-Yao Hsueh ◽  
Liang Zhou
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Cox Regression ◽  
External Validation ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Clinical Samples ◽  
Prognostic Signature

Abstract Background A growing body of evidence has suggested the involvement of metabolism in the occurrence and development of tumors. But the link between metabolism and laryngeal squamous cell carcinoma (LSCC) has rarely been reported. This study seeks to understand and explain the role of metabolic biomarkers in predicting the prognosis of LSCC. Methods We identified the differentially expressed metabolism-related genes (MRGs) through RNA-seq data of TCGA (The Cancer Genome Atlas) and GSEA (Gene set enrichment analysis). After the screening of protein-protein interaction (PPI), hub MRGs were analyzed by least absolute shrinkage and selection operator (LASSO) and Cox regression analyses to construct a prognostic signature. Kaplan–Meier survival analysis and the receiver operating characteristic (ROC) was applied to verify the effectiveness of the prognostic signature in four cohorts (TCGA cohort, GSE27020 cohort, TCGA-sub1 cohort and TCGA-sub2 cohort). The expressions of the hub MRGs in cell lines and clinical samples were verified by quantitative reverse transcriptase PCR (qRT-PCR). The immunofluorescence staining of the tissue microarray (TMA) was carried out to further verify the reliability and validity of the prognostic signature. Cox regression analysis was then used to screen for independent prognostic factors of LSCC and a nomogram was constructed based on the results. Results Among the 180 differentially expressed MRGs, 14 prognostic MRGs were identified. A prognostic signature based on two MRGs (GPT and SMS) was then constructed and verified via internal and external validation cohorts. Compared to the adjacent normal tissues, SMS expression was higher while GPT expression was lower in LSCC tissues, indicating poorer outcomes. The risk score proved the prognostic signature as an independent risk factor for LSCC in both internal and external validation cohorts. A nomogram based on these results was developed for clinical application. Conclusions Differentially expressed MRGs were found and proven to be related to the prognosis of LSCC. We constructed a novel prognostic signature based on MRGs in LSCC for the first time and verified via different cohorts from both databases and clinical samples. A nomogram based on this prognostic signature was developed.

scholarly journals CircRASSF2 promotes laryngeal squamous cell carcinoma progression by regulating the miR-302b-3p/IGF-1R axis

2019 ◽  
Vol 133 (9) ◽  
pp. 1053-1066 ◽  
Author(s):  
Linli Tian ◽  
Jing Cao ◽  
Hui Jiao ◽  
Jiarui Zhang ◽  
Xiuxia Ren ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Central Component ◽  
Reporter System

Abstract Background: Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) broadly expressed in cells of various species. However, the molecular mechanisms that link circRNAs with laryngeal squamous cell carcinoma (LSCC) are not well understood. In the present study, we attempted to provide novel basis for targeted therapy for LSCC from the aspect of circRNA–microRNA (miRNA)–mRNA interaction. Methods: We investigated the expression of circRNAs in three paired LSCC tissues and adjacent non-tumor tissues by microarray analysis. Differentially expressed circRNAs were identified between LSCC tissues and non-cancerous matched tissues, including 527 up-regulated circRNAs and 414 down-regulated circRNAs. We focused on hsa_circ_0059354, which is located on chromosome 20 and derived from RASSF2, and thus we named it circRASSF2. Results: circRASSF2 was found to be significantly up-regulated in LSCC tissues and LSCC cell lines compared with paired adjacent non-tumorous tissues and normal cells. Moreover, knockdown of circRASSF2 significantly inhibited cell proliferation and migration in vitro, which was blocked by miR-302b-3p inhibitor. Bioinformatics analysis predicted that there is a circRASSF2/miR-302b-3p/ insulin-like growth factor 1 receptor (IGF-1R) axis in LSCC progression. Dual-luciferase reporter system validated the direct interaction of circRASSF2, miR-302b-3p, and IGF-1R. Western blot verified that inhibition of circRASSF2 decreased IGF-1R expression. Furthermore, silencing circRASSF2 suppressed LSCC growth in vivo. Importantly, we demonstrated that circRASSF2 was up-regulated in serum exosomes from LSCC patients. Altogether, silencing circRASSF2 suppresses progression of LSCC by interacting with miR-302b-3p and decreasing inhibiting IGF-1R expression. Conclusion: In conclusion, these data suggest that circRASSF2 is a central component linking circRNAs to progression of LSCC via an miR-302b-3p/IGF-1R axis.

Development of an immunogenomics-based prognostic index model of laryngeal squamous cell carcinoma

2020 ◽  
Author(s):  
Yujie Shen ◽  
Han Zhou ◽  
Shikun Dong ◽  
Meiping Lu ◽  
Weida Dong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Cox Regression ◽  
Prognostic Index ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Cox Regression Analysis

Abstract Background: The immune system greatly affects the prognosis of various malignancies. Studies on differentially expressed immune-related genes (IRGs) in the immune microenvironment of laryngeal squamous cell carcinoma (LSCC) have rarely been reported.Methods: In this paper, the prognostic potentials of IRGs in LSCC were explored. The RNAseq dataset containing differentially expressed IRGs and corresponding clinical information of LSCC patients was obtained from The Cancer Genome Atlas (TCGA). A total of 371 up-regulated and 61 down-regulated IRGs were identified. Subsequent functional enrichment analysis revealed that the pathway of IRGs was mainly enriched in the cytokine-cytokine receptor interaction. Then, 30 IRGs with prognostic potentials in LSCC were screened out, and the regulatory network induced by relevant transcription factors (TFs) were constructed.Results: Finally, multivariate Cox regression analysis was conducted to assess the prognostic potential of 15 IRGs after adjustment of clinical factors and LSCC patients were classified into 2 subgroups based on different outcomes. The gene expression of the model was verified by other independent databases. Nomogram including the 15 IRGs signature was established and shown some clinical net beneft. Intriguingly, B cells were significantly enriched in the low-risk group. Conclusion:These findings may contribute to the development of potential therapeutic targets and biomarkers for the new-immunotherapy of LSCC.

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

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.

scholarly journals Plasma Cell-Free circRNAs Panel Act as Fingerprint Predicts the Occurrence of Laryngeal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Jiahui Han ◽  
Qiuhong Lin ◽  
Chunguang Dong
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Plasma Cell ◽  
Squamous Cell ◽  
Roc Curve ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Circular Rnas ◽  
Plasma Samples ◽  
Training Set ◽  
Potential Biomarker

Abstract Background: Circular RNAs (circRNAs) have recently emerged as a new class of RNAs, highly enriched in the human tissues and very stable within cells, exosomes and body fluids. In this study, we aimed to screen the plasma cell-free derived circRNAs in laryngeal squamous cell carcinoma (LSCC) and investigate whether these circRNAs could predicted LSCC as potential biomarkers. Methods: The circRNA microarray was employed with three samples in each group to screen the dysregulated circRNAs isolated from plasma samples. The top 20 circRNAs were first selected as candidates with the upregulated level in the plasma of LSCC. Results: Further validation found that only circ_0019201, circ_0011773 and circ_0122790 was consistent with training set. The ROC curve also revealed a high diagnostic ability an area under ROC curve value (AUC) for single circRNA and combined. The AUC for circ_0019201, circ_0011773 and circ_0122790 and the combined was 0.933, 0.908, 0.965 and 0.990 in training set. For the validation set, the AUC was 0.766, 0.864, 0.908 and 0.951. The three circRNAs were further investigated with stable expression in human plasma samples. Conclusions: The plasma derived circ_0019201, circ_0011773 and circ_0122790 might be the potential biomarker for predicting the LSCC.

scholarly journals Prognostic Value of Immune Associated Long Non-Coding RNAs In Laryngeal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Weixing Liu ◽  
Pei Li ◽  
Yue Liu ◽  
Zhiyuan Wang ◽  
Jiamin Liu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Cox Regression ◽  
Critical Role ◽  
Differentially Expressed ◽  
Prognostic Signature ◽  
Sequencing Data

Abstract Background: Increasing studies have demonstrated that immune associated lncRNAs (IALs) take an important part in the occurrence and development of multiple cancers. However, the prognosis value of IALs in laryngeal squamous cell carcinoma (LSCC) remains unexplored. This study aimed to evaluate the importance of IALs in LSCC. Methods: RNA sequencing data profiles of LSCC and clinical information of patients were obtained from TCGA dataset. Correlation analysis was performed to screen IALs. Then, a IALs based prognostic signature was constructed through univariate and multivariate Cox regression. The uncover molecular mechanisms of these selected IALs were explored by the bioinformatics analyses.Results: a total of seven differentially expressed survival-associated IALs were found in LSCC patients. a six IALs (LINC02154, SNHG12, CHKB-DT, AL158166.1, AC027307.2 and AL121899.1) based prognostic signature was established, which was a reliable tool to predict the prognosis of LSCC. The area under the curve (AUC) were 0.817 (one-year), 0.847 (three-year) and 0.895 (five-year). Further analysis, there were different infiltration of immune cells between low-risk and high-risk group patients. Additionally, a lncRNA-miRNA-mRNA regulatory network basted on six IALs, 75 miRNAs, and 156 differentially expressed mRNAs was constructed.Conclusions: IALs may play critical role in the occurrence and progression of LSCC, and the IALs based prognostic signature can predict the overall survival rate of LSCC.

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