Long Noncoding RNA CUDR Regulates HULC and β-Catenin to Govern Human Liver Stem Cell Malignant Differentiation

Gui, Xin; Li, Haiyan; Li, Tianming; Hu, Pu; Lu, Dongdong

doi:10.1038/mt.2015.166

Cited by 72 publications

(60 citation statements)

References 40 publications

(37 reference statements)

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“…What is more, miR-17-3p may also act independently of miR-17-3p, as it shares homology with a number of protein-coding genes such as TIMP3 (35) and MDM2 (36). In addition to miRNAs, lncRNAs could also be regulated by typical transcriptional factor (37,38), mRNA binding protein (39), promoter methylation (40), and histone acetylation levels (41). Our data revealed that GCASPC was upregulated by the histone deacetylase inhibitor TSA, suggesting that GCASPC expression in gallbladder cancer is likely to be regulated by histone acetylation.…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA GCASPC, a Target of miR-17-3p, Negatively Regulates Pyruvate Carboxylase–Dependent Cell Proliferation in Gallbladder Cancer

et al. 2016

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Long noncoding RNAs (lncRNA) are being implicated in the development of many cancers. Here, we report the discovery of a critical role for the lncRNA GCASPC in determining the progression of gallbladder cancer. Differentially expressed lncRNAs and mRNAs between gallbladder cancer specimens and paired adjacent nontumor tissues from five patients were identified and validated by an expression microarray analysis. Quantitative real-time PCR was used to measure GCASPC levels in tissues from 42 gallbladder cancer patients, and levels of GCASPC were confirmed further in a separate cohort of 89 gallbladder cancer patients. GCASPC was overexpressed or silenced in several gallbladder cancer cell lines where molecular and biological analyses were performed. GCASPC levels were significantly lower in gallbladder cancer than adjacent nontumor tissues and were associated with tumor size, American Joint Committee on Cancer tumor stage, and patient outcomes. GCASPC overexpression suppressed cell proliferation in vitro and in vivo, whereas GCASPC silencing had opposite effects. By RNA pull-down and mass spectrometry, we identified pyruvate carboxylase as an RNAbinding protein that associated with GCASPC. Because GCASPC is a target of miR-17-3p, we confirmed that both miR-17-3p and GCASPC downregulated pyruvate carboxylase level and activity by limiting protein stability. Taken together, our results defined a novel mechanism of lncRNA-regulated cell proliferation in gallbladder cancer, illuminating a new basis for understanding its pathogenicity. Cancer Res; 76(18); 5361-71. Ó2016 AACR.

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Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA GCASPC, a Target of miR-17-3p, Negatively Regulates Pyruvate Carboxylase–Dependent Cell Proliferation in Gallbladder Cancer

et al. 2016

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“…For examples, long noncoding RNA CUDR regulates HULC and β-Catenin to govern human liver stem cell malignant differentiation50. SET1A cooperates with CUDR to promote liver cancer growth and hepatocyte-like stem cell malignant transformation epigenetically51.…”

Section: Discussionmentioning

confidence: 99%

HULC cooperates with MALAT1 to aggravate liver cancer stem cells growth through telomere repeat-binding factor 2

Lin

et al. 2016

Sci Rep

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The dysregulation of lncRNAs has increasingly been linked to many human diseases, especially in cancers. Our results demonstrate HULC, MALAT1 and TRF2 are highly expressed in human hepatocellular carcinoma tissues, and HULC plus MALAT1 overexpression drastically promotes the growth of liver cancer stem cells. Mechanistically, both HULC and MALAT1 overexpression enhanced RNA polII, P300, CREPT to load on the promoter region of telomere repeat-binding factor 2(TRF2), triggering the overexpression, phosphorylation and SUMOylation of TRF2. Strikingly, the excessive TRF2 interacts with HULC or MALAT1 to form the complex that loads on the telomeric region, replacing the CST/AAF and recruiting POT1, pPOT1, ExoI, SNM1B, HP1 α. Accordingly, the telomere is greatly protected and enlonged. Furthermore, the excessive HULC plus MALAT1 reduced the methylation of the TERC promoter dependent on TRF2, increasing the TERC expression that causes the increase of interplay between TRET and TERC. Ultimately, the interaction between RFC and PCNA or between CDK2 and CyclinE, the telomerase activity and the microsatellite instability (MSI) are significantly increased in the liver cancer stem cells. Our demonstrations suggest that haploinsufficiency of HULC/MALAT1 plays an important role in malignant growth of liver cancer stem cell.

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“…As one of the promising novel biomarkers with high accuracy prognostic value for cancer patients, HULC has been noted to associate with diverse cellular processes, including migration, invasion, proliferation, differentiation, and apoptosis and are thereby prone to be involved in the tumorigenesis and progression [12, 14, 37, 38]. For example, HULC has been demonstrated to regulate hepatocellular cancer (HCC) proliferation through a miR-9-mediated RXRA signaling pathway or suppressing the expression of tumor suppressor p18 [39, 40].…”

Section: Discussionmentioning

confidence: 99%

“…Highly up-regulated in liver cancer (HULC), as one of the most up-regulated ncRNAs, was first identified from an HCC-specific gene expression profiling [11, 12]. Recently, many observations indicate that the striking promoted expression pattern was associated with worse survival and high risk of cancer metastasis in patients with various carcinomas [13, 14].…”

Section: Introductionmentioning

confidence: 99%

The Value of lncRNA HULC as a Prognostic Factor for Survival of Cancer Outcome: A Meta-Analysis

Chen

Liu

Hou

et al. 2017

Cell Physiol Biochem

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Aims: Growing evidence from recent studies has shown that lncRNA HULC plays a role in the development of multiple carcinomas. This meta-analysis aimed to analyze available data to identify the prognostic value of HULC in multiple tumors. Methods: A systematic search was performed by using PubMed (medline), Embase, ISI Web of Knowledge, Springer, the Cochrane Library, Scopus, BioMed Central, ScienceDirect, Wanfang, Weipu, and China National Knowledge Internet (CNKI) computerized databases from inception to Nov 30, 2016. The quality of the publications was assessed according to the critical review checklist of the Dutch Cochrane Centre proposed by MOOSE and PRISMA. Pooled hazard ratios (HR) with 95% confidence interval (95% CI) were calculated to summarize the effect. Results: A total of ten studies with 1077 cancer patients were pooled in the present meta-analysis to evaluate the prognostic value of HULC in multiple tumors. High expression levels of HULC were demonstrated to be associated with poor overall survival (OS) (HR=2.44, 95%CI: 1.96-3.03, P=0.000). Subgroup analysis showed that cancer type (digestive or non-digestive disease), residence region (China), sample size (more or less than 100) and follow-up months (more or less than 60) did not alter the predictive value of HULC on OS in various cancers. Additionally, increased HULC expression was found to be moderately associated with tumor stage and progression (III/IV vs. I/II: HR=1.59, 95% CI: 1.31-1.92, P<0.00001). Furthermore, elevated HULC expression significantly predicted distant metastasis (HR=3.90, 95% CI: 1.89-8.02, P=0.0002) and lymph node metastasis (HR=2.04, 95% CI: 1.03-4.05, P=0.04) respectively. No significant heterogeneity was observed among studies except lymph node metastasis. Conclusion: The results indicate that HULC expression level is an independent prognostic biomarker for unfavorable OS and metastasis in general tumors.

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Long Noncoding RNA CUDR Regulates HULC and β-Catenin to Govern Human Liver Stem Cell Malignant Differentiation

Cited by 72 publications

References 40 publications

Long Noncoding RNA GCASPC, a Target of miR-17-3p, Negatively Regulates Pyruvate Carboxylase–Dependent Cell Proliferation in Gallbladder Cancer

Long Noncoding RNA GCASPC, a Target of miR-17-3p, Negatively Regulates Pyruvate Carboxylase–Dependent Cell Proliferation in Gallbladder Cancer

HULC cooperates with MALAT1 to aggravate liver cancer stem cells growth through telomere repeat-binding factor 2

The Value of lncRNA HULC as a Prognostic Factor for Survival of Cancer Outcome: A Meta-Analysis

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