Abstract 4946: Aberrant methylations of microRNA-9s in lung cancers

Background: microRNAs (miRNAs) represent a new class of small non-coding RNAs regulating gene expression by inducing messenger RNA degradation or interfering with translation. miRNAs regulate many cellular processes and have been shown to be associated with cancer development. Recent study showed that miR-9s consisting of mir-9-1,9-2, 9-3 regulates E-cadherin. On the other hand, it has been reported that that methylation of miR-9s are associated with metastasis or poor prognosis of some type of human cancers. In this study, we examined the methylation status of miR -9-1, 9-2, 9-3 in lung cancer to find that miR-9 methylation seems to be associated with lymph node metastasis in lung cancer(LC). Material and methods: We collected 152 LC tumor DNAs which resected in our institute during 2007 to 2008. After bisulfate conversion, we determined the methylation status of miR-9-1, 9-2 and 9-3 by combined bisulfite restriction analysis method. Results: Aberrant methylations of either miR-9 were shown in 52 out of 152 cases (34%). Methylation of either miR-9 was present in 39 %, 26 %, 34 %, 42 % of males, females, never-smokers, and ever-smokers, respectively. Methylation of either miR-9s were detected in 35 % of adenocarcinomas, 33 % of squamous cell carcinomas, and 63 % of other LCs. Of note, miR-9 methylation was significantly more frequent in pathological stage I cases (39 %, n = 119) than in the other stage (II to IV) cases (18 %, n = 33; p = 0.028). While 4 cases were methylated in lymph node metastasis cases (17%, n =24), 48 cases were methylated in cases without lymph nodal metastasis (38 %, n =128 : p=0.06). Conclusion: Aberrant hypermetylation of miR-9s were associated with early pathological stage and /or non-lymph nodal metastasis, suggesting that miR-9s, which relate to aggressiveness and metastasis, might be sliced by abbarent methylation in early stage LCs. 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 4946. doi:10.1158/1538-7445.AM2011-4946