scholarly journals MiRNA expression profiling and emergence of new prognostic signature for oral squamous cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christo Rajan ◽  
V. G. Deepak Roshan ◽  
Imran Khan ◽  
V. G. Manasa ◽  
Iris Himal ◽  
...  

AbstractOral squamous cell carcinoma (OSCC), the most common type of head and neck cancers, is associated with high recurrence, metastasis, low long-term survival rates and poor treatment outcome. As deregulated miRNA expression plays a crucial role in malignant transformation and cancer progression, the present study is aimed at profiling the miRNA expression pattern in OSCC and developing a new miRNA prognostic signature for oral cancer. MiRNA expression profiling was performed using MiRNA microarray in 30 tumor and 18 normal samples. MiRNA signature obtained was validated with quantitative real time PCR (qRT-PCR) in 144 tumor and 36 normal samples. The potential targets, clinical implications and prognostic value of the miRNA signature were elucidated by various bioinformatics and statistical analyses. Microarray profiling identified a set of 105 miRNAs to be differentially expressed in OSCC, out of which a subset of 19 most dysregulated miRNAs were validated by qRT-PCR. In silico analysis revealed the signature miRNAs to be involved in various cancer associated pathways. Up-regulation of miR-196a, miR-21, miR-1237 and downregulation of miR-204, miR-144 was associated with poor prognosis of OSCC patients. The mir-196a/miR-204 expression ratio emerged as best predictor for disease recurrence and patient survival. Altogether, our study identified a miRNA signature for OSCC with prognostic significance.

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yilong Ai ◽  
Shiwei Liu ◽  
Hailing Luo ◽  
Siyuan Wu ◽  
Haigang Wei ◽  
...  

N6-Methyladenosine (m6A) modification is one of the commonest chemical modifications in eukaryotic mRNAs, which has essential effects on mRNA translation, splicing, and stability. Currently, there is a rising concern on the regulatory role of m6A in tumorigenesis. As a known component in the m6A methyltransferase complex, METTL3 (methyltransferase-like 3) plays an essential role in m6A methylation. Till now, the functions of METTL3 in oral squamous cell carcinoma (OSCC) and its relative mechanism remain to be explored. In this research, through the GEPIA database, we found that high METTL3 expression has a correlation with poor prognosis of squamous cell carcinoma of head and neck. qRT-PCR displayed that METTL3 was highly expressed in OSCC cells. Functionally, METTL3 knockdown reduced the invasion, migration, and proliferation competence of OSCC cells and attenuated the activation of CD8+ T cells. In contrast, METTL3 overexpression resulted in opposite results. GEPIA, UALCAN, and SRAMP databases, PCR, western blot, and m6A RNA methylation assay confirmed the m6A modification of PRMT5 and PD-L1 mediated by METTL3. In conclusion, our results displayed that METTL3 intensified the metastasis and proliferation of OSCC by modulating the m6A amounts of PRMT5 and PD-L1, suggesting that METTL3 may be a therapeutic target for OSCC patients.


2020 ◽  
Vol 68 (7) ◽  
pp. 1282-1288
Author(s):  
Hui Li ◽  
Junhong Jiang

Oral squamous cell carcinoma (OSCC) is a lethal malignancy. It is reportedly demonstrated that long non-coding RNA (lncRNA) participates in the development of OSCC. The purpose of this study was to clarify the function and possible molecular mechanisms of lncRNA MCM3AP antisense RNA 1 (lncRNA MCM3AP-AS1) in OSCC. Quantitative real-time PCR (qRT-PCR) was adopted to investigate MCM3AP-AS1 expressions in OSCC tissues and cells. The proliferation, migration and invasion of HN-6 and SCC-9 cells were probed by cell counting kit-8 and Transwell assays, respectively. Dual luciferase reporter gene assay, Pearson’s correlation analysis, qRT-PCR and western blot were used to detect the binding relationship among miR-204-5 p, MCM3AP-AS1 and forkheadbox C1 (FOXC1). MCM3AP-AS1 expression was elevated in OSCC tissues and cell lines. Overexpression of MCM3AP-AS1 facilitated the proliferation, migration and invasion of OSCC cells, while the knockdown of MCM3AP-AS1 suppressed these malignant phenotypes. Besides, MCM3AP-AS1 impeded miR-204-5 p by binding with it. MCM3AP-AS1 could also upregulate the expression of FOXC1 via repressing miR-204-5 p.MCM3AP-AS1 promotes the progression of OSCC cells by adsorbing miR-204-5 p and upregulating FOXC1 expressions.


2018 ◽  
Vol 120 (6) ◽  
pp. 9082-9090 ◽  
Author(s):  
Yanping Chen ◽  
Naiheng Hei ◽  
Jianguang Zhao ◽  
Shixiong Peng ◽  
Kaicheng Yang ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Yang-Yang Zhang ◽  
Ming-Hui Mao ◽  
Zheng-Xue Han

Objectives. Oral squamous cell carcinoma (OSCC) is the most common oral cancer and has a poor prognosis. We aimed to identify new biomarkers or potential therapeutic targets for OSCC. Materials and Methods. Four pairs of tumor and adjacent normal tissues were collected from OSCC patients, and differentially expressed genes (DEGs) were screened via high-throughput RNA sequencing (RNA-seq). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to analyze the DEGs. A protein-protein interaction (PPI) network was established with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape, and two significant clusters were found. Candidate genes were screened by analyzing head and neck squamous cell carcinoma (HNSCC) data from The Cancer Genome Atlas (TCGA). A DEG-based risk model was established to predict the overall survival (OS) of OSCC patients via Kaplan-Meier analysis and the log-rank test. Furthermore, univariate Cox regression analysis was applied to assess associations between potential biomarkers and the overall survival rate. Results. Of 720 total DEGs, fifty-two DEGs in the two subclusters of the PPI network analysis were selected. A risk model was established, and five candidate genes (SPRR2E, ICOS, CTLA4, HTR1D, and CCR4) were identified as biomarkers of OS in OSCC patients. Conclusions. We successfully constructed a prognostic signature to predict prognosis and identified five candidate genes associated with the OS of OSCC patients that are potential tumor biomarkers and targets in OSCC.


2016 ◽  
Vol 44 (7) ◽  
pp. 876-881 ◽  
Author(s):  
J. Moratin ◽  
S. Hartmann ◽  
R. Brands ◽  
M. Brisam ◽  
G. Mutzbauer ◽  
...  

2020 ◽  
Vol 10 ◽  
Author(s):  
Yanxiong Shao ◽  
Yuhan Song ◽  
Siming Xu ◽  
Siyi Li ◽  
Haiwen Zhou

BackgroundCircular RNAs (circRNAs) are involved in the pathogenesis of several diseases. Among oral maxillofacial cancers, oral squamous cell carcinoma (OSCC) has the highest incidence. However, the role of circRNAs in OSCC is still not clear. The aim of our study was to evaluate the circRNA expression profile in OSCC and explore further the potential role of circRNAs in the pathogenesis of OSCC.MethodsCircRNA sequencing was performed in 6 pairs of samples of OSCC and normal oral mucosal tissues. Expression of selected circRNAs was validated by qRT-PCR. GO and KEGG analyses were performed and binding relationships between circRNAs and miRNAs were predicted. The hsa_circ_0001766/miR-877-3p/VEGFA axis was selected to further elucidate its role in OSCC.ResultsWe showed that there were 122 differentially expressed (DE) circRNAs. Eight out of 10 selected circRNAs were validated by qRT-PCR. GO and KEGG analyses indicated that the identified DE circRNAs might be involved in the progression of OSCC. Then, after identification by Sanger sequencing and RNase R assay, the upregulated hsa_circ_0001766 was selected to investigate its potential role in OSCC. Bioinformatics analysis showed that hsa_circ_0001766 might act as a competing endogenous RNA (ceRNA) that sponged miR-877-3p to upregulate VEGFA expression. We selected OSCC cell lines SCC9 and SCC25. PCR results showed that the expression of hsa_circ_0001766 and VEGFA was upregulated in SCC9 and SCC25. Subsequently, using western blot, PCR, CCK8, and colony formation assays, we found that knocking down circRNA0001766 inhibited the expression of VEGFA and the proliferation of OSCC cells. Following this, miR-877-3p inhibitor reversed the inhibitory effect of si-hsa_circ_0001766 on expression of VEGFA and proliferation of OSCC cells.ConclusionsIn conclusion, our study revealed the possible role of circRNAs in the pathogenesis of OSCC, and identified the potential role of the hsa_circ_0001766/miR-877-3p/VEGFA axis in OSCC progression.


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