کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1946288 | 1054206 | 2016 | 11 صفحه PDF | دانلود رایگان |
• CCR492 regulates the cell-cycle progression.
• CCR492 has a cytoplasmic localization.
• CCR492 directly interacts with let-7 miRNAs.
• CCR492 by binding let-7 miRNAs, acts as ceRNA reducing the let-7 repressing activity on c-Myc.
• CCR492 contributes to cell transformation.
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 RNAs (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 (MEFs) 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.
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Journal: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms - Volume 1859, Issue 10, October 2016, Pages 1322–1332