Long noncoding RNAs as a novel component of the Myc transcriptional network

Winkle, Melanie; Berg, Anke van den; Tayari, Mina M.; Sietzema, Jantine; Terpstra, Martijn; Kortman, Gertrud; Jong, Debora de; Visser, Lydia; Diepstra, Arjan; Kok, Klaas; Kluiver, Joost

doi:10.1096/fj.14-263889

Cited by 51 publications

(61 citation statements)

References 49 publications

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“…The promoters of many lncRNAs are bound and regulated by transcription factors known to influence mRNA transcription, including cancer-related transcription factors, such as p53 [15, 16], Myc [17, 18] and E2F [19–22]. …”

Section: Introductionmentioning

confidence: 99%

A novel lncRNA, GASL1, inhibits cell proliferation and restricts E2F1 activity

et al. 2017

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The human genome encodes thousands of unique long non-coding RNAs (lncRNAs), many of which are emerging as critical regulators of cell fate. However, their functions as well as their transcriptional regulation are only partially understood. The E2F1 transcription factor induces both proliferation and apoptosis, and is a critical downstream target of the tumor suppressor, RB. Here, we provide evidence that a novel lncRNA named GASL1 is transcriptionally regulated by E2F1; GASL1 levels are elevated upon activation of exogenous E2F1 or endogenous E2Fs. Inhibition of GASL1 expression induced cell cycle progression, and in particular, G1 exit. Moreover, GASL1 silencing enhanced cell proliferation, while, conversely, its ectopic expression inhibited proliferation. Knockdown of GASL1 also enhanced E2F1-induced apoptosis, suggesting the existence of an E2F/GASL1 negative feedback loop. In agreement with this notion, silencing of GASL1 led to increased levels of phosphorylated pRB and loss of Rb impaired the effect of GASL1 silencing on G1 exit. Importantly, xenograft experiments demonstrated that GASL1 deletion enhances tumor growth. Moreover, low levels of GASL1 are associated with decreased survival of liver cancer patients. Taken together, our data identify GASL1 as a novel lncRNA regulator of cell cycle progression and cell proliferation with a potential role in cancer.

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Section: Introductionmentioning

confidence: 99%

A novel lncRNA, GASL1, inhibits cell proliferation and restricts E2F1 activity

et al. 2017

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“…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).…”

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confidence: 99%

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

Wang

Yang

Guang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Deregulated expression of c-Myc is an important molecular hallmark of cancer. The oncogenic function of c-Myc has been largely attributed to its intrinsic nature as a master transcription factor. Here, we report the long noncoding RNA (lncRNA) E2F1 messenger RNA (mRNA) stabilizing factor (EMS) as a direct c-Myc transcriptional target. EMS functions as an oncogenic molecule by promoting G1/S cell cycle progression. Mechanistically, EMS cooperates with the RNA binding protein RALY to stabilize E2F1 mRNA, and thereby increases E2F1 expression. Furthermore, EMS is able to connect c-Myc to cell cycle control and tumorigenesis via modulating E2F1 mRNA stability. Together, these findings reveal a previously unappreciated mechanism through which c-Myc induces E2F1 expression and also implicate EMS as an important player in the regulation of c-Myc function.

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“…MYC is a transcription factor involved in cell growth, proliferation and maintenance of stem cell-like properties 3,4 . Besides protein-coding genes, MYC also regulates the expression of multiple microRNAs (miRNAs) and long non-coding (lnc)RNAs 5,6 . In a previous study 7 , we identified a MYC-related miRNA expression profile in pediatric BL as compared to MYC-low chronic lymphocytic leukemia (CLL).…”

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confidence: 99%