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Regulation of ITGA3 by the anti‐tumor miR‐199 family inhibits cancer cell migration and invasion in head and neck cancer
- Source :
- Cancer Science
- Publication Year :
- 2017
- Publisher :
- John Wiley and Sons Inc., 2017.
-
Abstract
- For patients with head and neck squamous cell carcinoma (HNSCC), survival rates have not improved due to local recurrence and distant metastasis. Current targeted molecular therapies do not substantially benefit HNSCC patients. Therefore, it is necessary to use advanced genomic approaches to elucidate the molecular mechanisms underlying the aggressiveness of HNSCC cells. Analysis of our microRNA (miRNA) expression signature by RNA sequencing showed that the miR-199 family (miR-199a-5p, miR-199a-3p, miR-199b-5p and miR-199b-3p) was significantly reduced in cancer tissues. Ectopic expression of mature miRNA demonstrated that all members of the miR-199 family inhibited cancer cell migration and invasion by HNSCC cell lines (SAS and HSC3). These findings suggested that both passenger strands and guide strands of miRNA are involved in cancer pathogenesis. In silico database and genome-wide gene expression analyses revealed that the gene coding for integrin α3 (ITGA3) was regulated by all members of the miR-199 family in HNSCC cells. Knockdown of ITGA3 significantly inhibited cancer cell migration and invasion by HNSCC cells. Moreover, overexpression of ITGA3 was confirmed in HNSCC specimens, and high expression of ITGA3 predicted poorer survival of the patients (P = 0.0048). Our data revealed that both strands of pre-miR-199a (miR-199a-5p and miR-199a-3p) and pre-miR-199b (miR-199b-5p and miR-199b-3p) acted as anti-tumor miRNA in HNSCC cells. Importantly, the involvement of passenger strand miRNA in the regulation of cellular processes is a novel concept in RNA research. Novel miRNA-based approaches for HNSCC can be used to identify potential targets for the development of new therapeutic strategies.
- Subjects :
- 0301 basic medicine
Oncology
Male
Cancer Research
miR‐199b
Integrin alpha3
miR‐199a
Anti‐tumor
0302 clinical medicine
Cell Movement
Gene expression
Genetics, Genomics, and Proteomics
3' Untranslated Regions
Aged, 80 and over
Gene knockdown
General Medicine
Middle Aged
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms
030220 oncology & carcinogenesis
Carcinoma, Squamous Cell
Original Article
Female
ITGA3
Adult
medicine.medical_specialty
Biology
head and neck squamous cell carcinoma
03 medical and health sciences
Internal medicine
Cell Line, Tumor
microRNA
medicine
Humans
Computer Simulation
Neoplasm Invasiveness
Gene
Aged
Sequence Analysis, RNA
Squamous Cell Carcinoma of Head and Neck
Cancer
Original Articles
medicine.disease
Head and neck squamous-cell carcinoma
stomatognathic diseases
MicroRNAs
030104 developmental biology
Cell culture
Ectopic expression
Subjects
Details
- Language :
- English
- ISSN :
- 13497006 and 13479032
- Volume :
- 108
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Cancer Science
- Accession number :
- edsair.doi.dedup.....e7e81f477248bea02cdeaf375a6c83de