MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that negatively regulate the expression of their target genes. They are involved in many biological processes, including cell proliferation, apoptosis and differentiation, and are considered as promising new therapeutic targets for cancer. However, the identity of miRNAs involved in apoptosis and their respective targets remain largely unknown. Given the elevated complexity of miRNA regulation of gene expression, we performed a functional screening as an alternative strategy to identify those miRNAs that in lung cancer cells may interfere with the apoptotic process. To this aim we generated a derivative of the non-small cell lung carcinoma A549 cell line in which caspase-8, a critical upstream initiator of apoptosis, can be activated by the administration of the small dimerizer drug AP20187. We found a number of miRNAs that may rescue cell viability from caspase-8 activation. They included miRNAs already described as oncogenic such as miR-17, miR-135, miR-520, but also some miRNAs such as miR-124a and miR-34c for which a tumor suppressive role has been instead described or expected. Among them, miR-34c-5p markedly increased resistance to paclitaxel induced apoptosis. We demonstrate that Bmf (Bcl-2 modifying factor) is a target of miR-34c-5p and that its silencing, together with that of c-myc, a known target of miR-34c-5p, contributes to resistance to apoptosis induced by paclitaxel via p53 downregulation.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 192. doi:1538-7445.AM2012-192

©2012 American Association for Cancer Research
2012