MicroRNA-664 functions as an oncogene in cutaneous squamous cell carcinomas (cSCC) via suppressing interferon regulatory factor 2.
BACKGROUND
Aberrant expression of microRNA-664 was involved in tumor growth and metastasis of various cancers. The specific role of miR-664 in cutaneous squamous cell carcinoma (cSCC) is yet to be elucidated.


OBJECTIVE
The present study aimed to investigate the molecular mechanisms underpinning of cSCC development and provide translational insights for future therapeutics.


METHODS
Human cSCC specimens were used to determine the miR-664 by in situhybridization and IRF2 by immunohistochemistry. To study the potential mechanisms in tumorigenesis, three cSCC cell lines including HSC-5, HSC-1 and A431 as well as BALB/C mouse tumor model was utilized.


RESULTS
We found that miR-664 was remarkably high in cSCC patient specimens and cSCC cell lines. Overexpression of miR-664 promotes tumorigenic behaviors such as increased cell proliferation, migration and invasion capacities in vitro and enhanced tumorigenicity in xenograft mouse model. Our data further identified IRF2 as a direct downstream target of miR-664. Knockdown of IRF2 reverses pro-tumorigenesis phenotype of miR-664; whereas IRF2 over-expression inhibits miR-664 tumorigenesis in cSCC. Together, it revealed miR-664 functions as an oncogene in cSCC via suppression of IRF2.


CONCLUSION
Our data demonstrates that aberrant expression of miR-664 plays a critical role in carcinogenesis of cSCC. The discovery of novel targets such as miR-664 and IRF2 will facilitate future development of therapeutic interventions.
['Li|Xiangzhi|X|', 'Zhou|Cheng|C|', 'Zhang|Chen|C|', 'Xie|Xiongxiong|X|', 'Zhou|Zhaoming|Z|', 'Zhou|Meijuan|M|', 'Chen|Longhua|L|', 'Ding|Zhenhua|Z|']
D000818:Animals D063646:Carcinogenesis D002294:Carcinoma, Squamous Cell D045744:Cell Line, Tumor D049109:Cell Proliferation D015972:Gene Expression Regulation, Neoplastic D055785:Gene Knockdown Techniques D006801:Humans D050836:Interferon Regulatory Factor-2 D008297:Male D051379:Mice D035683:MicroRNAs D009857:Oncogenes D012867:Skin D012878:Skin Neoplasms D023041:Xenograft Model Antitumor Assays
MicroRNA-664 Cutaneous squamous cell carcinomas Interferon regulatory factor 2 Metastasis Proliferation Carcinogenesis