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| Status |
Public on Jun 08, 2014 |
| Title |
MicroRNA expression profile in Head and Neck Cancer: HOX-cluster embedded microRNA-196 and microRNA-10b dysregulation is implicated in cell proliferation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Non-coding RNA profiling by array
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| Summary |
Current evidence implicates aberrant microRNA expression patterns in human malignancies; measurement of microRNA expression may have diagnostic and prognostic applications. Roles for microRNAs in head and neck squamous cell carcinomas (HNSCC) are largely unknown. HNSCC, a smoking-related cancer, is one of the most common malignancies worldwide but reliable diagnostic and prognostic markers have not been discovered so far. Some studies have evaluated the potential use of miRNAs as biomarkers with clinical application in HNSCC. MicroRNA expression profile of oral squamous cell carcinoma samples was determined by means of DNA microarrays. We also performed gain-of-function assays for two differentially expressed miRNAs using two squamous cell carcinoma cell lines and normal oral keratinocytes. The effect of the over-expression of these molecules was evaluated by means of global gene expression profiling and cell proliferation assessment. Altered microRNA expression was detected for a total of 72 microRNAs. Among these we found well studied molecules, such as the miR-17-92 cluster, comprising potent oncogenic miRNAs, and miR-34, recently found to interact with p53. HOX-cluster embedded miR-196a/b and miR-10b were up- and down-regulated, respectively, in tumor samples. Since validated HOX gene targets for these microRNAs are not consistently deregulated in HNSCC, we performed gain-of-function experiments, in an attempt to outline their possible role. Our results suggest that both molecules interfere in cell proliferation through distinct processes, possibly targeting a small set of genes involved in cell cycle progression.Functional data on miRNAs in HNSCC is still scarce. Our data corroborate current literature and brings new insights into the role of microRNAs in HNSCC. We also show that miR-196a and miR-10b, not previously associated with HNSCC, may play an oncogenic role in this disease through the deregulation of cell proliferation. The study of microRNA alterations in HNSCC is an essential step to the mechanistic understanding of tumor formation and could lead to the discovery of clinically relevant biomarkers.
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| Overall design |
[miRNA] Sixteen patients with Oral Squamous Cell Carcinoma (OSCC) were selected for microarray experiments. Tumor and corresponding cancer free surgical margins were collected from patients submitted to surgical resection of primary tumor. MiR expression profiling was performed using the Illumina miR arrays version 1.0. The preparation and hybridization of the samples was done using the reagents and instructions supplied by the manufacturer.
[mRNA] We performed gain-of-function experiments in two human squamous cell carcinoma cell lines formicroRNAs miR-10b and in nomral keratinocytes for miR-196. In an attempt to outline their function we employed whole genome microarray expression profiling in order to identify genes affected by the over-expression of each microRNA. Cells transfected with synthetic precursor molecules were compared with transfection controls in terms of gene expression levels.
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| Contributor(s) |
Severino P, Brüggemann H, Borges F, Pereira WO, Andreghetto FM, Camps C, de Fatima Garrido Klingbeil M, de Oliveira Pereira W, Soares RM, Moyses R, Wünsch-Filho V, Mathor MB, Nunes FD, Ragoussis J, Tajara EH |
| Citation(s) |
24209638 |
| Submission date |
Aug 09, 2011 |
| Last update date |
Oct 04, 2023 |
| Contact name |
Patricia Severino |
| E-mail(s) |
patricia.severino@einstein.br
|
| Phone |
5511984661282
|
| Organization name |
Hospital Israelita Albert Einstein
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| Department |
Albert Einstein Research and Education Institute
|
| Street address |
Rua Comendador Elias Jafet, 755
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| City |
Sao Paulo |
| State/province |
Sao Paulo |
| ZIP/Postal code |
05653-000 |
| Country |
Brazil |
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| Platforms (3) |
| GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
| GPL9770 |
Illumina miR arrays version 1.0 |
| GPL10332 |
Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Feature Number version) |
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| Samples (42)
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| Relations |
| BioProject |
PRJNA145847 |
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