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Identification of oral carcinoma miRNA involved in Wnt/b-catenin signaling

ABSTRACT: MicroRNAs (miRNAs) participate in many biological processes and have emerged as key players in carcinogenesis. In order to identify changes in miRNAs specific for betelquid-associated oral squamous cell carcinoma (OSCC), we investigated the expression profiles of 858 miRNAs in a panel of 40 pairs of OSCC specimens and their matched non-tumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared to the matched tissue. Among these miRNAs, 19 downregulated miRNAs located in the chromosome 14q32.2 miRNA cluster region were analyzed. This miRNA cluster resides within a parentally imprinted region known to be important in development and growth. The re-expression of miR-329 and miR-410from this cluster significantly reduced OSCC cell proliferation and invasion and downregulated Wnt-7b, an activator of the Wnt/b-catenin pathway. Furthermore, the expression of those 2 miRNAs was restored by 5-aza-2′-deoxycytidine treatment and the expression levels of the 2 miRNAs were inversely correlated with the hypermethylation of the Meg-3 promoter in OSCC cells. Specifically, arecoline, a major betel nut alkaloid, reduces miR-329 and miR-410 expression. Our results thus provide a novel molecular insight into how betel quid may contribute to oral carcinogenesis through the epigenetic silencing of tumor suppressor miRNAs targeting the Wnt/b-catenin signaling pathway.

ORGANISM(S): Homo sapiens

PROVIDER: GSE45238 | GEO | 2015/01/07

SECONDARY ACCESSION(S): PRJNA193307

REPOSITORIES: GEO

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Identification of oral carcinoma miRNA involved in Wnt/b-catenin signaling

Project description:MicroRNAs (miRNAs) participate in many biological processes and have emerged as key players in carcinogenesis. In order to identify changes in miRNAs specific for betelquid-associated oral squamous cell carcinoma (OSCC), we investigated the expression profiles of 858 miRNAs in a panel of 40 pairs of OSCC specimens and their matched non-tumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared to the matched tissue. Among these miRNAs, 19 downregulated miRNAs located in the chromosome 14q32.2 miRNA cluster region were analyzed. This miRNA cluster resides within a parentally imprinted region known to be important in development and growth. The re-expression of miR-329 and miR-410from this cluster significantly reduced OSCC cell proliferation and invasion and downregulated Wnt-7b, an activator of the Wnt/b-catenin pathway. Furthermore, the expression of those 2 miRNAs was restored by 5-aza-2′-deoxycytidine treatment and the expression levels of the 2 miRNAs were inversely correlated with the hypermethylation of the Meg-3 promoter in OSCC cells. Specifically, arecoline, a major betel nut alkaloid, reduces miR-329 and miR-410 expression. Our results thus provide a novel molecular insight into how betel quid may contribute to oral carcinogenesis through the epigenetic silencing of tumor suppressor miRNAs targeting the Wnt/b-catenin signaling pathway. Total RNA was obtained from 40 pairs of OSCC patients with tumor specimens and their adjacent non-tumorous epithelia.

2015-01-07 | E-GEOD-45238 | biostudies-arrayexpress

Whole-transcriptome analyses identify critical differentially expressed mRNAs, miRNAs, lncRNAs, and circRNAs during the process of oral carcinogenesis

Project description:Oral carcinogenesis is a multi-step process involving normal mucosa progressing to oral precancerous lesions and finally to oral squamous cell carcinoma (OSCC). This complex process encompasses various molecules, including non-coding RNAs (ncRNAs). In this study, we performed whole-transcriptome analyses on adjacent normal tissues, oral leukoplakia tissues, and OSCC tissues, with the goal of identifying key differentially expressed circRNAs, lncRNAs, miRNAs, and mRNAs associated with different stages of oral carcinogenesis. In our study, numerous differentially expressed circRNAs, lncRNAs, miRNAs, and mRNAs were identified in adjacent normal, oral leukoplakia, and OSCC tissues. Subsequently, we constructed two regulatory competitive endogenous RNA (ceRNA) networks and identified some potential critical molecules involved in oral carcinogenesis. In conclusion, based on the whole-transcriptome analyses, we mapped the molecular feathers at RNA level during the process of oral carcinogenesis and revealed certain ncRNAs with great research potential.

2023-10-26 | GSE246050 | GEO

A three–microRNA signature as a potential biomarker for the early detection of oral cancer

Project description:Background: Oral squamous cell carcinoma (OSCC) is often diagnosed at a late stage and may be malignantly transformed from oral leukoplakia (OL). This study aimed to identify potential plasma microRNAs (miRNAs) for the early detection of oral cancer. Methods: Plasma from normal, OL, and OSCC patients were evaluated. Small RNA sequencing was used to screen differently expressed miRNAs among the groups. Next, these miRNAs were validated with individual samples by quantitative real-time polymerase chain reaction (qRT-PCR) assays. The possible physiological roles of the identified miRNAs were further investigated using bioinformatics analysis. Results: Three miRNAs (miR-222-3p, miR-150-5p, and miR-423-5p) were identified as differentially expressed among groups; miR-222-3p and miR-423-5p negatively correlated with T stage, lymph node metastasis status, and clinical stage. A high diagnostic accuracy (Area under curve = 0.88) was demonstrated for discriminating OL from OSCC. Bioinformatics analysis reveals that miR-423-5p and miR-222-3p are significantly over-expressed in oral cancer tissues and involved in various cancer pathways. Conclusions: The three plasma miRNA panel may be useful to monitor malignant progression from OL to OSCC and as potential biomarkers for early detection of oral cancer.

2018-04-17 | GSE104440 | GEO

WNT3 Promotes Chemoresistance in Oral Squamous Cell Carcinoma via Activating the Canonical β-catenin Pathway

Project description:Oral squamous cell carcinoma (OSCC) represents a major malignancy in the oral and maxillofacial region. The primary therapeutic agents, 5-fluorouracil (5FU) and oxaliplatin (OXA), often encounter the challenge of chemoresistance, leading to treatment failure. The WNT/β-catenin signaling pathway, closely tied with chemoresistance, offers a promising therapeutic avenue. This study delves into this potential connection. 5FU-resistant and OXA-resistant cell lines were established by gradually elevating the drug concentration in the culture medium. Differential gene expressions between parental and resistant cells were analyzed by RNA sequencing analysis, which was then substantiated via RT-qPCR and western blot. The influence of the WNT signaling on OSCC drug resistance was ascertained through WNT3 knockdown or overexpression. The WNT inhibitor, MSAB, was probed for its capacity to boost the efficacy of 5FU or OXA. Through transcriptome sequencing, successfully derived 5FU-resistant and OXA-resistant cell lines revealed a conspicuous activation of the WNT/β-catenin signaling pathway in the drug-resistant cells. WNT3 was identified as a pivotal factor contributing to chemoresistance in OSCC. Counteracting β-catenin notably augmented the therapeutic potency of 5FU and OXA. Our study underscored the activation of the WNT/β-catenin signaling pathway in resistant OSCC cell lines. By modulating WNT signaling activity, drug resistance in OSCC cells may be effectively circumvented.

2024-05-15 | GSE248792 | GEO

Real-time quantitative PCR analysis of 232 microRNAs in human oral tissues

Project description:Oral squamous cell carcinoma (OSCC) is the sixth most common cause of cancer mortality worldwide, and the five-year survival rate remains low in patients with advanced OSCC. Many studies indicate that microRNAs (miRNAs) may paly critical roles in OSCC carcinogenesis, but the dynamic composition and functions of miRNAs-mRNAs regulatory networks in OSCC pathogenesis remain largely unknown. Thus, detailed investigations of OSCC-associated miRNAs and their regulated networks may provide insights into mechanistic understanding of OSCC progression and development of new strategies of OSCC management. To this end, we first sought to compile from a systems perspective the miRNA-mRNA networks underlying OSCC pathogenesis. Our targeted, qRT-PCR-based expression profiling of 232 miRNAs in 49 human oral tissue samples (including 19 normal and 30 OSCC specimens) identified 49 differentially expressed miRNAs (p-value < 0.01 and fold change > 2) in OSCC tissues.

2017-09-18 | GSE103931 | GEO

Spatial Multi-omics Reveals the Heterogeneity of Tumor Microenvironment in the OSF-Associated OSCC

Project description:Oral submucous fibrosis (OSF) is one of the most common precancerous malignant orders (PMO) with high rates exacerbating into oral squamous cell carcinoma (OSCC), mostly occurred in patients with chewing betel-nut habits in Southeast Asia and Pacific region. However, the spatial characteristics and heteogeneities of tumor microenvironment (TME) in OSF-associated OSCC still remains unclear. Here, we characterized the spatiotemporal changes of OSF-associated OSCC at different malignant states by performing 10x Visium Spatial Transcriptomics (ST) sequencing and airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) analysis.

2024-03-05 | GSE220978 | GEO

Methylation profiling of oral squamous cell carcinoma (OSCC)

Project description:According to epidemiological studies, a vast majority, approximately 80%~90% of male OSCC patients in Taiwan habitually drink alcohol (A), and chew betel quid (B), and use cigarette (C). To assess the impact of these dietary factors on the epigenome, we conduct a high-throughput screen survey in an oral cancer cohort with exposure of A, B, and C. Results indicate aberrent methylation patterns are prevalent in OSCC patients with ABC risk factors. Genomic DNA was collected from tumor and non-tumor pair-wise samples. These biopsies were obtained from 40 male OSCC patients who regularly drink alcohol, chew areca nut and smoking.

2015-04-01 | E-GEOD-38532 | biostudies-arrayexpress

Downregulation of miR-218-5p promotes invasion of oral squamous cell carcinoma cells via activation of CD44-ROCK signaling

Project description:The invasion front of oral squamous cell carcinoma (OSCC) harbors the most aggressive cells of the tumor and is critical for cancer invasion and metastasis. MicroRNAs (miRNAs) play an important role in regulating OSCC invasion. In this study, we modeled the OSCC invasion front on a microfluidic chip and investigated differences in miRNA profiles between cells in the invasion front and those in the tumor mass by small RNA sequencing and bioinformatic analysis. We found that miR-218-5p was downregulated in invasion front cells; a luciferase reporter assay confirmed that cluster of differentiation (CD)44 was a direct target of miR-218-5p. Inhibiting miR-218-5p in invasion front cells activated CD44- Rho-associated protein kinase (ROCK) signaling and promoted cell invasion by inducing cytoskeletal reorganization. These findings indicate that miR-218-5p negatively regulates OSCC invasiveness by targeting the CD44–ROCK pathway and may be a useful therapeutic target for OSCC. Moreover, our method of modeling and isolating invasion front cells using a microfluidic chip is a time-saving alternative to in vivo models.

2018-05-21 | GSE107243 | GEO

Affymetrix SNP array data for oral squamous cell carcinoma and oral dysplasia samples

Project description:The development of oral squamous cell carcinoma (OSCC) is a multistep process requiring the accumulation of genetic alterations. Oral carcinogenesis is a multifactorial process involving numerous genetic changes that affect the activity of oncogenes, tumor suppressor genes and other classes of disease-related genes.Therefore, to identify the responsive genes for progression of oral dysplasia or OSCC, we here performed CGH analysis to DNA from oral dysplasia and OSCC by microdissection Copy number analysis of Affymetrix 250K SNP arrays was performed for 8 oral dysplasia samples, 8 oral squamous cell carcinoma samples, using microdissection

2013-10-22 | E-GEOD-51265 | biostudies-arrayexpress

Gene expression profiling of oral squamous cell carcinoma (OSCC)

Project description:According to epidemiological studies, a vast majority, approximately 80%~90% of male OSCC patients in Taiwan habitually drink alcohol (A), and chew betel quid (B), and use cigarette (C). To assess the impact of these dietary factors on the transcriptom, we conduct a high-throughput screen survey in an oral cancer cohort with exposure of A, B, and C. Results indicate several potential oncogenes and tumor suppressor genes are dysregulated in OSCC patients with ABC risk factors. Total RNA was collected from tumor and non-tumor pair-wise samples. These biopsies were obtained from 40 male OSCC patients who regularly drink alcohol, chew areca nut and smoking.

2013-05-02 | E-GEOD-37991 | biostudies-arrayexpress

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