Oral cancer is a subtype of head and neck cancer, the eighth common cancer type in the world. MicroRNAs (miRNAs) are small non-coding RNAs that mediate gene expression at the post-transcriptional level by degrading target messenger RNA or repressing their translation. The deregulation of certain microRNAs has been associated with the progression and metastasis of various cancer types. A total of 133 miRs were dysregulated in oral cancer cells when compared with normal oral keratinocytes by using microRNA microarray hybridization. Among them, miR-22, often silenced in breast cancer, colon cancer, and multiple myeloma, is downregulated and least known in oral carcinogenesis. In this study, we confirmed the down-regulation of miR-22 in the majority of oral cell lines and 70 % of the tested clinical specimens, as measured by real-time PCR. Both gain-of-function and loss-of-function experiments showed that increased miR-22 expression significantly reduced oral cancer cell migration and invasion, whereas decreased miR-22 expression dramatically enhanced cell migration and invasion. Snail, a transcription factor that promotes cell invasion and tumor metastasis, was predicted to be a target of miR-22. The prediction was validated by the inverse correlation of miR-22 and snail protein, and the luciferase reporter assay bearing 3’- translated region derived from snail. Silencing snail expression by using shRNA recapitulated the anti-metastatic function of miR-22, whereas restored snail expression attenuated the function of miR-22 in oral cancer cells. Together, these results suggest that miR-22 may act as a tumor suppressor through decreasing snail expression in oral cancer and thus be used as a therapeutic target to block oral cancer metastasis. Citation Format: Yi-Zih Kuo, Yun-Chu Huang, Yuh-Ling Chen, Hung-I Lo, Sen-Tien Tsai, Chi-Wu Chiang, Li-Wha Wu. Identification of dysregulated miRs and its target genes in head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4195. doi:10.1158/1538-7445.AM2013-4195