AB74. MicroRNAs fuels cancer growth through the RNAa mechanism

Abstract

MicroRNAs (miRNAs) are master regulators of gene expression and have been known to be involved in cancer by acting either as tumor suppressors or oncomiRs. It is widely accepted that the miRNAs carry out their functions in the cytoplasm via targeting the 3’ UTR region of mRNAs leading to downregulation of gene expression. However, whether and how miRNAs function in the nucleus remains largely unknown. We showed that both exogenous and endogenous miRNAs are able to induce the expression of genes whose promoters contain the targets of the miRNAs, a phenomenon known as RNA activation (RNAa). In mouse prostate cancer cells, two miRNAs (miR-744 and miR-1186) are able to stimulate cell cycle progression and cause chromosomal instability by inducing the expression of Cyclin B1, a gene critical for mitosis. Genome-wide analysis of potential miRNA binding in human prostate cancer cells further revealed that the miRNA machinery interacts with the transcriptional apparatus to sustain the expression of hundreds of genes which are important for cell proliferation, evading apoptosis, angiogenesis and DNA damage repair. These findings suggest that miRNAs could be implicated in carcinogenesis through a non-canonical miRNA targeting mechanism.