ABSTRACT
MicroRNAs (miRNAs) can act not only as tumor suppressor genes but also as oncogenes. Oncogenic miRNAs (oncomiRs) could therefore provide opportunities for the treatment of human malignancies. Here, we aimed to identify oncomiRs present in oral squamous cell carcinoma (OSCC) and addressed whether targeting these miRNAs might be useful in treatment for cancer. Functional screening for oncomiRs in a human OSCC cell line (GFP-SAS) was carried out using the miRCURY LNA microRNA Knockdown Library - Human version 12.0. We identified a locked nucleic acid (LNA)/DNA antisense oligonucleotide against miR-361-3p (LNA-miR-361-3p) which showed the largest degree of growth inhibition of GFP-SAS cells. Transfection with a synthetic mimic of mature miR-361-3p resulted in an approximately 20% increase in the growth of GFP-SAS cells. We identified odd-skipped related 2 (OSR2) as a miR-361-3p target gene. Transfection of GFP-SAS cells with LNA-miR-361-3p caused a significant increase in the expression levels of OSR2. Cotransfection of a OSR2 3'-UTR luciferase reporter plasmid and LNA-miR-361-3p into GFP-SAS cells produced higher levels of luciferase activity than in cells cotransfected with the LNA-nontarget. We assessed the effect of LNA-miR-361-3p on the in vivo growth of GFP-SAS cells. We found that LNA-miR-361-3p significantly reduced the size of s.c. xenografted GFP-SAS tumors, compared to the control group treated with LNA-NT. Finally, we observed that miR-361-3p is overexpressed in OSCC tissues. These results suggest that miR-361-3p supports the growth of human OSCC cells both in vitro and in vivo and that targeting miR-361-3p could be a useful therapeutic approach for patients with OSCC.
