Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
Volume 1859, Issue 10, Pages 1322-1332Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagrm.2016.06.010
Keywords
Non-coding RNA; c-Myc; Let-7; ceRNA; Cell cycle
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Funding
- Associazione Italiana Ricerca sul Cancro (AIRC) [IG 2014/15217]
- Epigenomics Flagship Project EPIGEN
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In mammals 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 RNA5 (lincRNAs), potentially involved in the control of the cell-cycle progression. We identified 10 novel lincRNAs expressed in response to serum treatment in mouse embryonic fibroblasts (MEF5) and in BALB/c fibroblasts, comparably to early genes. By loss-of-function experiments we found that lincRNA CCR492 is required for G1/S progression, localizes in the cell cytoplasm and contains 4 let-7 microRNA recognition elements (MREs). Mechanistically, CCR492 functions as a competing endogenous RNA (ceRNA) to antagonize the function of let-7 microRNAs, leading to the de-repression of c-Myc. Moreover, we show that ectopic expression of CCR492 along with a constitutively active H-Ras promotes cell transformation. Thus, we identified a new lincRNA expressed as an early gene in mammalian cells to regulate the cell-cycle progression by upregulating c-Myc expression. (C) 2016 Elsevier B.V. All rights reserved.
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