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.

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