mir-105, mir-185 and let-7a overexpression experiment (CBX79). unidentified

ABSTRACT: Background MicroRNAs (miRNAs) are short single stranded noncoding RNAs that use base pairing between a 'seed' region and complementary target sites in a messenger RNA to direct translational repression and degradation of target mRNAs. They play key roles in development, differentiation, and metabolism. Chromosomal alterations are common in cancer and amplification or deletion of miRNAs located in these regions may be involved in carcinogenesis. Results Here we present the identification of multiple miRNAs localized in chromosomal regions commonly altered in human lung cancers. Introduction of two such miRNAs, miR-107 and -185, suppressed growth of the human lung adenocarcinoma cell lines (H1299 and A549). Flow cytometry analysis revealed both hsa-miR-107 and hsamiR- 185 induce a G1 cell cycle arrest in H1299 cells. Using microarrays, we find hundreds of genes are affected by transfection of these miRNAs, and for mir-107 large numbers of the down-regulated genes are annotated with the gene ontology term 'cell cycle'. The sets of genes affected by both miRNAs are only partly overlapping and mir-185 down-regulated genes were not enriched for the term cell-cycle suggesting an alternative pathway to G1 arrest. Conclusions Using miRNA-target predictions and the array data we identify a cohort of likely direct targets of miR-107 and -185 for G1 cell cycle arrest in human lung cancer cells and validate a subset including CDK6. These miRNAs may contribute to the suppression of lung carcinogenesis through G1 arrest induction.