The long intergenic non-coding RNA CCR492 functions as a let-7 competitive endogenous RNA to regulate c-Myc expression. Mus musculus

The cell cycle progression through the G1 phase is a tightly regulated process mediated by the transcriptional activation of early genes in response to mitogenic stimuli, whose dysregulation often leads to tumorigenesis. We here report the discovery by RNA-seq of cell cycle regulated (CCR) long intergenic non-coding RNAs (lincRNAs), potentially involved in the control of the cell cycle progression. We identified 10 new lincRNAs whose expression was induced in response to serum treatment in mouse embryonic fibroblasts (MEF) and in Balb/c fibroblasts, comparably to early genes. By loss-of-function experiments we found that lincRNA CCR492 is required for cell cycle progression, localizes in the cell cytoplasm and contains 4 let-7 miRNA recognition elements (MREs). Mechanistically, CCR492 functions as a competing endogenous RNA (ceRNA) to antagonize the function of Let-7 microRNA, leading to the de-repression of c-Myc. Moreover, we show that ectopic expression of CCR492 along with a constitutively active H-Ras triggers cell transformation. In brief, we found a novel lincRNA that regulates c-Myc expression, is required for efficient progression of the cell cycle, and whose deregulation contributes to tumour growth. Overall design: Expression profiling by high-throughput sequencing