Dataset Information

The role of long non-coding RNAs in the pathogenesis of head and neck squamous cell carcinoma.

ABSTRACT: Head and neck cancers are a heterogeneous collection of malignancies of the upper aerodigestive tract, salivary glands, and thyroid. However, the molecular mechanisms underlying the carcinogenesis of head and neck squamous cell carcinomas (HNSCCs) remain poorly understood. Over the past decades, overwhelming evidence has demonstrated the regulatory roles of long non-coding RNAs (lncRNAs) in tumorigenesis, including HNSCC. Notably, these lncRNAs have vital roles in gene regulation and affect various aspects of cellular homeostasis, including proliferation, survival, and metastasis. They exert regulating functions by interacting with nucleic acids or proteins and affecting cancer cell signaling. LncRNAs represent a burgeoning field of cancer research, and we are only beginning to understand the importance and complicity of lncRNAs in HNSCC. In this review, we summarize the deregulation and function of lncRNAs in human HNSCC. We also review the working mechanism of lncRNAs in HNSCC pathogenesis and discuss the potential application of lncRNAs as diagnostic/prognostic tools and therapeutic targets in human HNSCC.

SUBMITTER: Jiang M

PROVIDER: S-EPMC8717422 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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The role of long non-coding RNAs in the pathogenesis of head and neck squamous cell carcinoma.

Jiang Man M Liu Fang F Yang An-Gang AG Wang Wei W Zhang Rui R

Molecular therapy oncolytics 20211206

Head and neck cancers are a heterogeneous collection of malignancies of the upper aerodigestive tract, salivary glands, and thyroid. However, the molecular mechanisms underlying the carcinogenesis of head and neck squamous cell carcinomas (HNSCCs) remain poorly understood. Over the past decades, overwhelming evidence has demonstrated the regulatory roles of long non-coding RNAs (lncRNAs) in tumorigenesis, including HNSCC. Notably, these lncRNAs have vital roles in gene regulation and affect vari ...[more]

PMID: 35024439

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Project description:Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis. Considerable evidence indicates that autophagy and non-coding RNA play essential roles in the biological processes involved in cancers, but associations between autophagy-related long non-coding RNAs (lncRNAs) and HNSCC remain unclear. In the present study, HNSCC RNA sequences and autophagy-related gene data were extracted from The Cancer Genome Atlas database and the Human Autophagy Database. A total of 1,153 autophagy-related lncRNAs were selected via calculating Pearson's correlation coefficient. Three prognosis-related autophagy lncRNAs were identified via univariate Cox regression, least absolute shrinkage and selection operator analysis, and multivariate Cox regression analysis. We also constructed a prognostic model based on these autophagy-related lncRNAs and evaluated its ability to accurately and independently predict the prognosis of HNSCC patients. The area under the curve (AUC) was 0.864 (3-year) and 0.836 (5-year), and our model can independently predict the prognosis of HNSCC. The prognostic value of the three autophagy lncRNAs was confirmed via analysis of samples from five databases. To further identify the functions of the three lncRNAs, a co-expression network was constructed and pathway analysis was performed. In that analysis the lncRNAs were correlated with 189 related genes and 20 autophagy-related genes, and these lncRNAs mainly involved homologous recombination, the Fanconi anemia pathway, the autophagy-related pathway, and immune-related pathways. In addition, we validated the expression levels of three lncRNAs and autophagy markers (ATG12, BECN1, and MAP1LC3B) based on TIMER, Oncomine, and HPA database analysis. Our results indicated that TTTY15 was increased in HPV positive and HPV negative HNSCC patients, and three autophagy markers were up-regulated in all HNSCCC patients. Lastly, association between three lncRNAs and autophagy markers was performed, and our results showed that TTTY15 and MIF-AS1 were associated with autophagy markers. Collectively, these results suggested that three autophagy-related lncRNAs have prognostic value in HNSCC patients.

Project description:BackgroundThis study aimed to develop multi-RNA-based models using a competing endogenous RNA (ceRNA) regulatory network to provide survival risk prediction in head and neck squamous cell carcinoma (HNSCC).MethodsAll long non-coding RNA (lncRNA), microRNA (miRNA), and mRNA expression data and clinicopathological features related to HNSCC were derived from The Cancer Genome Atlas. Differentially expressed RNAs were calculated using R. Prognostic factors were identified using univariate Cox regression analysis. Functional analysis was performed using GO, KEGG pathways, and PPI network. Based on the results, we derived a risk signature and compared high- and low-risk subgroups using LASSO regression analysis. Survival analysis and the relationship between risk signature and clinicopathological features were performed using log-rank tests and Cox regression analysis. A ceRNA regulatory network was constructed, and prognostic lncRNAs and miRNA expression levels were validated in vitro and in vivo.ResultsA list of 207 lncRNAs, 18 miRNAs and 362 mRNAs related to overall survival was established. Five lncRNAs (HOTTIP, LINC00460, RMST, SFTA1P, and TM4SF19-AS1), one miRNA (hsa-miR-206), and one mRNA (STC2) were used to construct the ceRNA network. Three prognostic models contained 13 lncRNAs, eight miRNAs, and 17 mRNAs, which correlated with the patient status, disease-free survival (DFS), stage, grade, T stage, N stage, TP53 mutation status, angiolymphatic invasion, HPV status, and extracapsular spread. KEGG pathway analysis revealed significant enrichment of "Transcriptional misregulation in cancer" and "Neuroactive ligand-receptor interaction." In addition, HOTTIP, LINC00460, miR-206 and STC2 were validated in GTEx data, GEO microarrays and six HNSCC cell lines.ConclusionsOur findings clarify the interaction of ceRNA regulatory networks and crucial clinicopathological features. These results show that prognostic biomarkers can be identified by constructing multi-RNA-based prognostic models, which can be used for survival risk prediction in patients with HNSCC.

Dataset Information

The role of long non-coding RNAs in the pathogenesis of head and neck squamous cell carcinoma.

Publications

The role of long non-coding RNAs in the pathogenesis of head and neck squamous cell carcinoma.

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