Abstract B2-03: Inferred miRNA activity identifies miRNA-mediated regulatory networks underlying multiple cancers

Abstract

Abstract MicroRNAs (miRNAs) play a key role in regulating tumor progression and metastasis. However, miRNA's activity can't be measured by its expression level. We developed a computational approach, ActMiR, for identifying active miRNAs and miRNA-mediated regulatory mechanisms. Applying ActMiR to four cancer datasets in The Cancer Genome Atlas (TCGA), we showed that (1) miRNA activity was tumor subtype specific; (2) genes correlated with inferred miRNA activities were more likely to enrich for miRNA binding motifs; (3) expression levels of these genes and inferred miRNA activities were more likely to be negatively correlated. For the four cancer types in TCGA we identified 64~203 key miRNAs for each cancer subtype and annotated their biological functions. For ER-/HER2- breast cancers we identified activities of key miRNAs let-7d and miR-18a as potential prognostic markers and validated them in two independent ER-/HER2- breast cancer data sets. We experimentally validated their causal relationships with their target genes. Similarly, we showed that key miRNA activities but no miRNA expression level were consistently associated with clinical outcomes for other cancer types. Taken together, the inferred activity of key miRNA provided a functional link to its mediated regulatory network, and can be used to robustly predict patient's survival. Citation Format: Eunjee Lee, Koichi Ito, Eric E. Schadt, Hanna Y. Irie, Jun Zhu. Inferred miRNA activity identifies miRNA-mediated regulatory networks underlying multiple cancers. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-03.