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

Wang, Chenfeng; Yang, Yang; Guang, Zhang; Li, Jingxin; Wu, Xianning; Ma, Xiaoling; Ge, Shengfang; Mei, Yide

doi:10.1073/pnas.1903432116

Cited by 65 publications

(63 citation statements)

References 73 publications

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“…expression peaked in G1 phase, and its knockdown gave growth inhibition in all four cell lines, enrichment of cells in the G1 phase by 3-7 percentage points and a corresponding reduction of cells present in the S phase. These results are in line with a previous functional study of RP11−132A1.4 in A549 cells[47]. In addition to reporting similar growth inhibition and enrichment of cells in G1 phase, the study revealed that RP11−132A1.4, there named E2F1 mRNA stabilizing (EMS) lncRNA, is a direct transcriptional target of c-MYC.…”

supporting

confidence: 91%

Joint changes in RNA, RNA polymerase II, and promoter activity through the cell cycle identify non-coding RNAs involved in proliferation

Hegre

Samdal

Klima

et al. 2021

Preprint

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Proper regulation of the cell cycle is necessary for normal growth and development of all organisms. Conversely, altered cell cycle regulation often underlies proliferative diseases such as cancer. Long non-coding RNAs (lncRNAs) are recognized as important regulators of gene expression and are often found dysregulated in diseases, including cancers. However, identifying lncRNAs with cell cycle functions is challenging due to their often low and cell-type specific expression. We present a highly effective method that analyses changes in promoter activity, transcription, and RNA levels for identifying genes enriched for cell cycle functions. Specifically, by combining RNA sequencing with ChIP sequencing through the cell cycle of synchronized human keratinocytes, we identified 1009 genes with cell cycle-dependent expression and correlated changes in RNA polymerase II occupancy or promoter activity as measured by histone 3 lysine 4 trimethylation (H3K4me3). These genes were highly enriched for genes with known cell cycle functions and included 59 lncRNAs. We selected four of these lncRNAs (AC005682.5, RP11-132A1.4, ZFAS1, and EPB41L4A-AS1) for further experimental validation and found that knockdown of each of the four lncRNAs affected cell cycle phase distributions and reduced proliferation in multiple cell lines. These results show that many genes with cell cycle functions have concomitant cell-cycle dependent changes in promoter activity, transcription, and RNA levels and support that our multi-omics method is well suited for identifying lncRNAs involved in the cell cycle.

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supporting

confidence: 91%

Joint changes in RNA, RNA polymerase II, and promoter activity through the cell cycle identify non-coding RNAs involved in proliferation

Hegre

Samdal

Klima

et al. 2021

Preprint

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“…3A, B), we hypothesized that TANAR could modulate TWIST1 mRNA stability via the TANAR-TWIST1 interaction, as was shown with the presence of TANAR in TWIST1 pull-down assay (See Fig. 3E) (43,45,46). Indeed, mRNA stability assay, using treatment with Actinomycin, revealed that knocking down TANAR could block the overexpressing AR-increased TWIST1 mRNA stability (Fig.…”

Section: Mechanism Dissection Of How Tanar Can Alter Twist1 Expressiomentioning

confidence: 65%

Androgen Receptor promotes renal cell carcinoma (RCC) vasculogenic mimicry (VM)viaaltering TWIST1 nonsense-mediated decay through lncRNA-TANAR

You

Sun

Liu

et al. 2020

Preprint

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AbstractWhile the androgen receptor (AR) may influence the progression of clear cell renal cell carcinoma (ccRCC), its role to impact vasculogenic mimicry (VM) to alter the ccRCC progression and metastasis remains obscure. Here we demonstrated that elevated AR expression was positively correlated with tumor-originated vasculogenesis in ccRCC patients. Consistently, in vitro research revealed AR promoted VM formation in ccRCC cell lines via modulating lncRNA-TANAR/TWIST1 signals. Mechanism dissection showed that AR could increase lncRNA-TANAR (TANAR) expression through binding to the androgen response elements (AREs) located on its promoter region. Moreover, we found that TANAR could impede nonsense-mediated mRNA decay (NMD) of TWIST1 mRNA by direct interaction with TWIST1 5’UTR. A preclinical study using in vivo mouse model with orthotopic xenografts of ccRCC cells further confirmed the in vitro data. Together, these results illustrated that AR-mediated lnc-TANAR signals might play a crucial role in ccRCC VM formation and metastasis, and targeting this newly identified AR/lncRNA-TANAR/TWIST1 signaling may help in the development of a novel anti-angiogenesis therapy to better suppress the ccRCC progression.

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“…As with the protein-coding transcripts, the transcription of lncRNAs is also controlled by the transcriptional factors. 28 , 29 As an example, lncRNA HAS2 - AS1 was upregulated by transcription factor cAMP responsive element-binding protein1 in epithelial ovarian cancer, and then promoted the tumorigenesis of epithelial ovarian cancer by regulating miR-466 / RUNX family transcription factor 2 axis. 30 Recently, STAT3 has been reported to play an important role in various malignancies.…”

Section: Discussionmentioning

confidence: 99%

<p>STAT3-Induced Upregulation of lncRNA CASC9 Promotes the Progression of Bladder Cancer by Interacting with EZH2 and Affecting the Expression of PTEN</p>

Yuan¹,

Sun²,

Du³

et al. 2020

OTT

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Long non-coding RNA (lncRNA) cancer susceptibility candidate 9 (CASC9) has been reported to play a vital role in tumorigenesis. This study explored the biological role of CASC9 and its regulation mechanism in bladder cancer (BC). Methods: Gene expression was evaluated using quantitative reverse transcription polymerase chain reaction and Western blot. The functional role of CASC9 in BC was studied using Cell Counting Kit-8, colony formation assay, scratch wound healing assay, transwell invasion assay, and xenograft tumor assay. In addition, the mechanism of CASC9 function in BC was determined using RNA immunoprecipitation assay and chromatin immunoprecipitation assay. Results: CASC9 was upregulated in BC tissues and cell lines, and correlated with the staging and metastasis in BC. Knockdown of CASC9 inhibited the proliferation, migration, and invasion of BC cells. Similarly, silencing of CASC9 inhibited tumor growth in vivo. Signal transducer and activator of transcription 3 (STAT3) was upregulated in BC tissues and cell lines, and positively correlated with CASC9 in BC tissues. Moreover, CASC9 was shown to be regulated by STAT3 in BC cells. Furthermore, CASC9 regulated phosphatase and tensin homolog (PTEN) expression by interacting with enhancer of zeste homolog 2 (EZH2). More significantly, CASC9 silencing-mediated inhibition of BC progression was partly reversed by EZH2 overexpression or PTEN inhibition. Conclusion: Upregulation of CASC9 induced by STAT3 promoted the progression of BC by interacting with EZH2 and affecting the expression of PTEN, representing a novel regulatory mechanism for BC progression.

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

Cited by 65 publications

References 73 publications

Joint changes in RNA, RNA polymerase II, and promoter activity through the cell cycle identify non-coding RNAs involved in proliferation

Joint changes in RNA, RNA polymerase II, and promoter activity through the cell cycle identify non-coding RNAs involved in proliferation

Androgen Receptor promotes renal cell carcinoma (RCC) vasculogenic mimicry (VM)viaaltering TWIST1 nonsense-mediated decay through lncRNA-TANAR

<p>STAT3-Induced Upregulation of lncRNA CASC9 Promotes the Progression of Bladder Cancer by Interacting with EZH2 and Affecting the Expression of PTEN</p>

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