Abstract Background: Dysregulation of miRNA expression has been identified in a number of cancers and an accumulating data indicate that some miRNAs can function as tumor suppressors or oncogenes and are important in cancer development. Deletion or loss of function of a tumor-suppressing miRNA results in overexpression of target oncogenes. Conversely, activation or overexpression of an oncogenic miRNA results in silencing of tumor-suppressing target genes. According to miRNA profiles on microarray, miR-99b was down-expressed in Korean lung cancer. FGFR-3 is predicted target of miR-99b through two public algorithms. FGFR-3 has been demonstrated to be involved in the RAS/RAF/MEK/MAPK pathway through activation of p90 ribosomal S6 kinase. It has been reported that FGFRs are frequently overexpressed in NSCLC cell lines, suggesting that an FGFR-dependent autocrine signaling pathway may operate in a subset of NSCLCs. Material & method: We studied expression of miR-99b and FGFR-3 using quantitative reverse transcription PCR (qRT-PCR) in lung cancer tissue. To examine whether miR-99b could regulate FGFR-3 in lung cancer, we performed transient transfection of pre-miR-99b into lung cancer cell line, then we performed qRT-PCR and western blot in HCC1438, HCC95, and H522 cells for analysis of FGFR-3 expression. We hypothesized the miR-99b has a role of inhibitor cell growth in lung cancer. To test this hypothesis, we performed cell proliferation assay. Results: miR-99b was down-regulated and FGFR-3 was up-regulated in lung cancer. Over-expression of miR-99b induced marked reduction of FGFR-3 mRNA levels and protein level in lung cancer cell line HCC1438, HCC95, and H522. The growth rate in miR-99b precursor treated cell was lower than in negative control of miR treated cell. Conclusion: Abnormal down-regulation of miR-99b could lead to the over-expression of FGFR-3 in lung cancer. miR-99b may be a potent tumor suppressor and may be a potential candidate of therapeutic tool in lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4003. doi:10.1158/1538-7445.AM2011-4003