Abstract
Long non-coding RNA (lncRNA) can act as ceRNA to regulate the expression of target genes by sponging miRNAs, and therefore plays an essential role in tumor initiation and progression. However, functional roles and regulatory mechanisms of lncRNAs as ceRNAs in head and neck squamous cell carcinoma (HNSCC) remain to be determined. We downloaded RNA sequence profiles from The Cancer Genome Atlas (TCGA) database, and identified the differential RNAs by bioinformatics. Then we analyzed the biological processes of differential expressed RNAs (DER), and established their interaction networks and pathway analysis to find out potential biological effects of these DERs. Besides, we also explored the relationship between the DERs and prognosis of HNSCC patients. We obtained 525 tumor samples and 44 paracancerous controls, and there were 1081 DElncRNAs, 1889 DEmRNAs, and 145 DEmiRNAs. GO and KEGG pathways analysis of these DEmRNAs were mainly involved in “Protein digestion and absorption,” “Calcium signaling pathway,” and “ECM-receptor interaction.” The analysis of the ceRNA network identified 61 DElncRNAs as functional ceRNAs whose dysregulated expression may affect the expression of oncogenes/tumor suppressor genes. Furthermore, univariate and multivariate Cox regression analysis revealed that 4 DElncRNAs, 3 EDmiRNAs, and 6 DEmRNAs can predict survival with high accuracy. Survival analysis found that 4 lncRNAs was related to prognostic, including overexpressed RP11-366H4.1, HOTTIP, RP11-865I6.2, and RP11-275N1.1 patients had a worse survival. In conclusion, through constructing the ceRNA network in HNSCC patients, we identified key lncRNA-miRNA-mRNA network in HNSCC. All the DERs might participate in varieties of pathways in the initiation, progression, and invasion of HNSCC. Furthermore, some miRNAs (hsa-mir-99a, hsa-mir-337, and hsa-mir-137) and mRNAs (NOSTRIN, TIMP4, GRB14, HOXB9, CELSR3, and ADGRD2) may be the prognostic genes of HNSCC. This study provided a new target and theoretical basis for further research on molecular mechanisms and biomarkers.
Highlights
Head and neck cancer refers to malignant tumors derived from the nasal cavity, paranasal sinuses, nasopharynx, oral cavity, pharynx, and larynx; the majority of these tumors are squamous cell carcinomas and their carcinogenesis has been associated with cigarette smoking (Hashibe et al, 2009), alcoholism (Hashibe et al, 2009) and HPV (Herrero et al, 2003)
Non-coding RNAs can be divided into microRNA and long noncoding RNA according to the transcript size (Derrien et al, 2012)
RNA-sequencing data of 546 samples with head and neck squamous cell carcinoma (HNSCC) were retrieved from the The Cancer Genome Atlas (TCGA) data portal1
Summary
Head and neck cancer refers to malignant tumors derived from the nasal cavity, paranasal sinuses, nasopharynx, oral cavity, pharynx, and larynx; the majority of these tumors are squamous cell carcinomas and their carcinogenesis has been associated with cigarette smoking (Hashibe et al, 2009), alcoholism (Hashibe et al, 2009) and HPV (Herrero et al, 2003). Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with an incidence of over 650 000 new cases each year (Torre et al, 2015). It has been demonstrated that non-coding RNAs play important roles in regulating gene expression (Wang and Chang, 2011). Plenty of studies have discovered that miRNAs can post-transcriptionally inhibit translation or repress mRNAs expression through binding to the 3 -untranslated region (3 -UTR) of the target genes (Chan and Wang, 2015), leading to cleavage of target mRNAs and/or inhibition of their translation. It is widely accepted that miRNAs may act as oncogenes or suppressor genes during tumor initiation and progression
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