Dataset Information

MicroRNAs and Long Non-Coding RNAs as Regulators of NANOG Expression in the Development of Oral Squamous Cell Carcinoma.

ABSTRACT: NANOG is a stem cell transcription factor that is believed to play an important role in the development of oral squamous cell carcinoma (OSCC), but there is limited data regarding the role of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the regulation of NANOG expression. We therefore analyzed expression of NANOG, NANOG-regulating miRNAs and lncRNAs in OSCC cancerogenesis, using oral biopsy samples from 66 patients including normal mucosa, dysplasia, and OSCC. Expression analysis of NANOG, miR-34a, miR-145, RoR, SNHG1, AB209630, and TP53 was performed using qPCR and immunohistochemistry for NANOG protein detection. NANOG protein showed no staining in normal mucosa, very weak in low-grade dysplasia, and strong staining in high-grade dysplasia and OSCC. NANOG, miR-145, RoR, and SNHG1 showed up-regulation, TP53 and miR-34a showed down-regulation, and AB209630 showed variable expression during cancerogenesis. NANOG mRNA was up-regulated early in cancerogenesis, before strong protein expression can be detected. NANOG was in correlation with miR-145 and RoR. Our results suggest that miRNAs and lncRNAs, particularly miR-145 and RoR, might be important post-transcription regulatory mechanisms of NANOG in OSCC cancerogenesis. Furthermore, NANOG protein detection has a diagnostic potential for oral high-grade dysplasia, distinguishing it from low-grade dysplasia and non-neoplastic reactive lesions.

SUBMITTER: Grubelnik G

PROVIDER: S-EPMC7906007 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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MicroRNAs and Long Non-Coding RNAs as Regulators of NANOG Expression in the Development of Oral Squamous Cell Carcinoma.

Grubelnik Gašper G Boštjančič Emanuela E Aničin Aleksandar A Dovšak Tadej T Zidar Nina N

Frontiers in oncology 20210211

NANOG is a stem cell transcription factor that is believed to play an important role in the development of oral squamous cell carcinoma (OSCC), but there is limited data regarding the role of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the regulation of NANOG expression. We therefore analyzed expression of NANOG, NANOG-regulating miRNAs and lncRNAs in OSCC cancerogenesis, using oral biopsy samples from 66 patients including normal mucosa, dysplasia, and OSCC. Expression analysis of ...[more]

PMID: 33643897

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Project description:Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide, due to poor diagnosis and treatment. There is increasing evidence that demonstrates the involvement of long non-coding RNAs (lncRNAs) in carcinogenesis and cancer progression. Therefore, the aim of the present study was to explore potential lncRNA-associated features of patients with OSCC as a valuable and independent prognostic biomarker. A total of 268 lncRNA expression profiles and clinical patient information on OSCC were downloaded from The Cancer Genome Atlas database. The clinical information was exploited for prescreening, using Cox regression analysis, and differentially expressed lncRNAs (DElncRNAs) were identified using edgeR software. Using the 'caret' package, the datasets were categorized into test datasets and training datasets, respectively. Through bioinformatics, seven prognostic DElncRNAs were selected. Using the regression coefficients, a risk score based on the seven-DElncRNA signature was developed to assess the prognostic function of key DElncRNAs. According to the median risk score, patients were classified into high-risk and low-risk groups in the training and test datasets. Additionally, receiver operating characteristic (ROC) curve analysis was conducted to evaluate the sensitivity and specificity of the prognostic DElncRNAs, and the optimal cut-off point was obtained from ROC analysis. Based on the optimal cut-off point, the patients were also categorized into high-risk and low-risk groups. Notably, the optimal cut-off point was more sensitive than the median risk score, particularly in the test dataset. The Kaplan-Meier survival and log rank test analysis results indicated that the P-value, based on the optimal cut-off, was less than the median risk cut-off. Additionally, stratified analysis results revealed that the seven-DElncRNAs signature was also independent of OSCC age. Furthermore, the findings of the present study suggested that the seven-DElncRNA signature can be used as a potential prognostic indicator and may have important clinical significance in OSCC.

Project description:Background and objectiveOral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck, and its morbidity and mortality are increasing year by year. Changes in key genes are thought to be closely related to the occurrence and development of OSCC. Pyroptosis is an inflammatory form of programmed cell death that has been implicated in malignancies and inflammatory diseases. Changes in the expression of long noncoding RNAs may also affect tumorigenesis and progression. In this study, our main objective was to evaluate the association between pyroptosis-related lncRNAs and prognosis in patients with OSCC.MethodsThe RNA-seq data and clinicopathological data of OSCC patients are from The Cancer Genome Atlas database. The pyroptosis gene set is obtained from Gene Set Enrichment Analysis database. Univariate COX, Lasso and multivariate COX regression analyses were used for the construction of risk prognostic models of OSCC, eight lncRNAs were incorporated into prognostic models. The Kaplan-Meier method and log-rank test were used to evaluate the differences of overall survival between patients in high-risk and low-risk groups. The reliability of predictions across the dataset was analyzed by receiver operating characteristic (ROC) curves. The immune signature score was calculated using the single-sample gene set enrichment analysis.ResultsEight pyroptosis-related lncRNAs were used to construct prognostic signature of OSCC, including AC136475.2, AC024075.2, JPX, ZFAS1, TNFRSF10A-AS1, LINC00847, AC099850.3 and IER3-AS1. According to this prognostic signature, patients with OSCC were divided into high-risk and low-risk groups. Kaplan-Meier survival analysis showed that the survival rate of the high-risk group was significantly lower than the low-risk group. ROC area for risk score was 0.716, and ROC area of the 8 lncRNAs are all between 0.5 and 1, implied that these lncRNAs had high accuracy in predicting the prognosis of OSCC patients. Immune Infiltration findings suggested that these lncRNAs affected immune responses in the microenvironment of OSCC.ConclusionThe prognostic signature based on pyroptosis-related lncRNAs potentially serves as an independent prognostic indicator for OSCC patients. And this signature facilitates research on targeted diagnosis and treatment of patients diagnosed with OSCC.

Dataset Information

MicroRNAs and Long Non-Coding RNAs as Regulators of NANOG Expression in the Development of Oral Squamous Cell Carcinoma.

Publications

MicroRNAs and Long Non-Coding RNAs as Regulators of NANOG Expression in the Development of Oral Squamous Cell Carcinoma.

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