Background: The down-regulation of microRNA subsets could imply a tumor suppressor function, which is often observed in tumor development. MicroRNA-137 has been found to be down-regulated in colorectal cancer, glioblastoma multiforme, oral cancer, and squamous cell carcinoma of the head and neck. Some recent studies show that DNA methylation contributes to down-regulation of microRNA-137 during tumorigenesis. The purpose of the study was to investigate the significance of microRNA-137 promoter methylation in lung cancer. Methods: Several lung cancer cell lines were treated with DNA methyltransferase inhibitor (5-Aza) and/or HDAC inhibitor (trichostatin A) whether microRNA-137 could be reactivated. From pared tumor and adjacent non-tumor lung tissues, real-time RT-PCR for the microRNA-137 expression, quantitative methylation specific PCR for the methylation analysis, and bisulfite modified DNA sequencing for the validation were used for the study. Results: MicroRNA-137 was reactivated by treatment with DNA methyltransferase inhibitor (5-Aza) and/or HDAC inhibitor (trichostatin A) in lung cancer cell lines. Quantitative methylation specific PCR showed increased MIR137 promoter methylation in lung cancer tissues compared with adjacent non-tumor tissues, which was further validated with bisulfite sequencing. Conclusion: The results of the study suggest that miR-137 is down-regulated in lung cancer mediated by promoter methylation.Background: The down-regulation of microRNA subsets could imply a tumor suppressor function, which is often observed in tumor development. MicroRNA-137 has been found to be down-regulated in colorectal cancer, glioblastoma multiforme, oral cancer, and squamous cell carcinoma of the head and neck. Some recent studies show that DNA methylation contributes to down-regulation of microRNA-137 during tumorigenesis. The purpose of the study was to investigate the significance of microRNA-137 promoter methylation in lung cancer. Methods: Several lung cancer cell lines were treated with DNA methyltransferase inhibitor (5-Aza) and/or HDAC inhibitor (trichostatin A) whether microRNA-137 could be reactivated. From pared tumor and adjacent non-tumor lung tissues, real-time RT-PCR for the microRNA-137 expression, quantitative methylation specific PCR for the methylation analysis, and bisulfite modified DNA sequencing for the validation were used for the study. Results: MicroRNA-137 was reactivated by treatment with DNA methyltransferase inhibitor (5-Aza) and/or HDAC inhibitor (trichostatin A) in lung cancer cell lines. Quantitative methylation specific PCR showed increased MIR137 promoter methylation in lung cancer tissues compared with adjacent non-tumor tissues, which was further validated with bisulfite sequencing. Conclusion: The results of the study suggest that miR-137 is down-regulated in lung cancer mediated by promoter methylation.