MicroRNA-122, an abundant and conserved liver-specific miRNA, regulates hepatic metabolism and functions as a tumor suppressor, yet systematic and direct biochemical elucidation of the miR-122 target network remains incomplete. To this end, we performed Argonaute crosslinking immunoprecipitation (Ago-CLIP) sequencing in miR-122 knockout and control mouse livers, as well as in matched human hepatocellular carcinoma (HCC) and benign liver tissue to identify miRNA target sites transcriptome-wide in two species. We observed a majority of miR-122 binding on 3’-UTRs and coding exons followed by extensive binding to other genic and non-genic sites. Motif analysis of miR-122 dependent binding revealed a novel G-bulged motif in addition to canonical motifs. A large number of miR-122 targets were found to be species-specific. Upregulation of several common mouse and human targets, most notably BCL9, predicted survival in HCC patients. These results broadly define the molecular consequences of miR-122 downregulation in hepatocellular carcinoma.
|Date made available||28 Mar 2017|
|Publisher||Gene Expression Omnibus|
Luna, J. (Creator), Barajas, J. M. (Creator), Teng, K. Y. (Creator), Sun, H. (Creator), Ghoshal, K. (Creator) (28 Mar 2017). Argonaute CLIP defines a deregulated miR-122 bound transcriptome that correlates with patient survival in human liver cancer (Mouse CLIP-Seq). Gene Expression Omnibus.