The interplay of long non-coding RNAs and MYC in cancer

Abstract

Long non-coding RNAs (lncRNAs) are a class of RNA molecules that are changing how researchers view eukaryotic gene regulation. Once considered to be non-functional products of low-level aberrant transcription from non-coding regions of the genome, lncRNAs are now viewed as important epigenetic regulators and several lncRNAs have now been demonstrated to be critical players in the development and/or maintenance of cancer. Similarly, the emerging variety of interactions between lncRNAs and MYC, a well-known oncogenic transcription factor linked to most types of cancer, have caught the attention of many biomedical researchers. Investigations exploring the dynamic interactions between lncRNAs and MYC, referred to as the lncRNA-MYC network, have proven to be especially complex. Genome-wide studies have shown that MYC transcriptionally regulates many lncRNA genes. Conversely, recent reports identified lncRNAs that regulate MYC expression both at the transcriptional and post-transcriptional levels. These findings are of particular interest because they suggest roles of lncRNAs as regulators of MYC oncogenic functions and the possibility that targeting lncRNAs could represent a novel avenue to cancer treatment. Here, we briefly review the current understanding of how lncRNAs regulate chromatin structure and gene transcription, and then focus on the new developments in the emerging field exploring the lncRNA-MYC network in cancer.

VIRMA-Dependent N6-Methyladenosine Modifications Regulate the Expression of Long Non-Coding RNAs CCAT1 and CCAT2 in Prostate Cancer

“…In fact, in our set of primary tissue samples we found a direct correlation between CCAT1/2 and MYC transcript levels, which plays an oncogenic role in PCa [49]. In view of these results and currently available data, we postulate that stabilization of CCAT1/2 by m 6 A has an amplifying effect on MYC expression levels in cancer cells via 2 separate mechanisms: (i) Directly, through both lncRNAs acting as super-enhancers that positively regulate MYC mRNA [21]; (ii) Indirectly, by means of CCAT1/2 acting as microRNA sponges for MYC-targeting microRNAs let-7A and miR-145, respectively [50][51][52][53] (Figure 8). Accordingly, a moderate but highly significant correlation between CCTA1/2 and MYC transcript expression was depicted in our clinical samples set.…”

“…Remarkably, other studies also demonstrated that CCAT1 or CCAT2 knockdown through siRNAs inhibit cell growth, migration, and invasion in PC-3 and DU145 cells [21,43], indicating that CCAT1/2 silencing mimics VIRMA knockdown in metastatic androgen-independent PCa cells.…”

“…Because lncRNA CCAT1 and CCAT2 are involved in regulation of proto-oncogene MYC [20,21], the link between VIRMA-dependent m 6 A-regulated lncRNAs and their ability to increase MYC expression was also tested in these patient samples. Remarkably, a moderate/weak positive correlation was observed between CCAT1/2 and MYC transcript levels (Spearman r = 0.3 p < 0.0001 for CCAT1; Spearman r = 0.4 p < 0.0001 for CCAT2).…”

LncRNA LINC00899 promotes progression of acute myeloid leukaemia by modulating miR‐744‐3p/YY1 signalling

“…[9][10][11][12] Their dysfunction and specific role in various diseases, especially cancer, have attracted more and more attention recently. [13][14][15] LncRNAs genomic mutants or alteration have been widely clarified to induce oncogenic effect in multiple cancer types, such as breast cancer, 16 colorectal cancer, 17 ovarian cancer, 18 gastric cancer, 19 lung cancer, 20 as well as AML. 21,22 Several lncRNAs, including lnc_071255/Pvt1, lnc_104449, or lnc_177417, are found essential for AML maintenance and normal differentiation.…”

Long noncoding RNA EMS connects c-Myc to cell cycle control and tumorigenesis

“…Although previous studies on c-Myc's transcriptional network have mainly focused on protein-coding genes, it has been increasingly recognized that c-Myc is also capable of regulating noncoding RNAs (26). These include both microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) (27)(28)(29)(30)(31)(32)(33)(34)(35). The lncRNAs are defined as non-protein-coding RNA transcripts longer than 200 nucleotides (nt) (36).…”