Natural antisense transcripts drive a regulatory cascade controlling c-MYC transcription

<p><i>Cis</i>-natural antisense transcripts (<i>cis-</i>NATs) are long noncoding RNAs transcribed from the opposite strand and overlapping coding and noncoding genes on the sense strand. <i>cis-</i>NATs are widely present in the human genome and can be involved in multiple mechanisms of gene regulation. Here, we describe the presence of <i>cis-</i>NATs in the 3′ distal region of the c-MYC locus and investigate their impact on transcriptional regulation of this key oncogene in human cancers. We found that <i>cis-</i>NATs are produced as consequence of the activation of cryptic transcription initiation sites in the 3′ distal region downstream of the c-MYC 3′UTR. The process is tightly regulated and leads to the formation of two main transcripts, NAT6531 and NAT6558, which differ in their ability to fold into stem-loop secondary structures. NAT6531 acts as a substrate for DICER and as a source of small RNAs capable of modulating c-MYC transcription. This complex system, based on the interplay between <i>cis</i>-NATs and NAT-derived small RNAs, may represent an important layer of epigenetic regulation of the expression of c-MYC and other genes in human cells.</p

Genes differentially expressed in short survival versus long survival patients, considered according to cancer type and cancer class.

Volcano plots showing significantly downregulated (the thresholds are FDR -0.5) genes in green and red, respectively. Here short survival patients are compared with long survival patients, so in all three panels genes found to be upregulated are genes that are upregulated in short survival patients, and genes found downregulated are genes that are downregulated in short survival patients. Grey indicates genes that are not significantly downregulated or upregulated. Log of fold change (LogFC) is on the x-axis and significance level (-log10P) is on the y-axis. Panel A shows differentially expressed genes when all of the patients are considered (n = 515). Panel B shows differentially expressed genes when only patients with solid cancers are considered (n = 293), and panel C shows differentially expressed genes when only patients with blood cancers are considered (n = 222). In all panels, the significantly downregulated and upregulated genes are labelled with their Hugo Gene Nomenclature Committee (HGNC) gene symbols. The three genes (SSX1, MAGEC2 and ULBP2) that are found to be significantly differentially expressed in all three analyses are shown in bold.</p

Patients statistics.

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