Long noncoding RNA, the methylation of genomic elements and their emerging crosstalk in hepatocellular carcinoma

Yuan, Shengxian; Zhang, Jin; Xu, Qingguo; Yang, Yuan; Zhou, Weiping

doi:10.1016/j.canlet.2015.08.008

Cited by 40 publications

(24 citation statements)

References 77 publications

(84 reference statements)

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“…LncRNAs can also combine and interact with proteins via protein scaffolding . It has also been reported that lncRNAs participate in the methylation regulatory network by epigenetically silencing their target gene . Due to the complex function of lncRNAs, we speculate that DANCR may down‐regulate miR‐496 via an undiscovered regulatory pathway.…”

Section: Discussionmentioning

confidence: 99%

LncRNA‐DANCR contributes to lung adenocarcinoma progression by sponging miR‐496 to modulate mTOR expression

Rui

Guo

et al. 2017

J Cellular Molecular Medi

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Long non‐coding RNAs (lncRNAs) have emerged as new and important regulators of pathological processes including tumour development. In this study, we demonstrated that differentiation antagonizing non‐protein coding RNA (DANCR) was up‐regulated in lung adenocarcinoma (ADC) and that the knockdown of DANCR inhibited tumour cell proliferation, migration and invasion and restored cell apoptosis rescued; cotransfection with a miR‐496 inhibitor reversed these effects. Luciferase reporter assays showed that miR‐496 directly modulated DANCR; additionally, we used RNA‐binding protein immunoprecipitation (RIP) and RNA pull‐down assays to further confirm that the suppression of DANCR by miR‐496 was RISC‐dependent. Our study also indicated that mTOR was a target of miR‐496 and that DANCR could modulate the expression levels of mTOR by working as a competing endogenous RNA (ceRNA). Furthermore, the knockdown of DANCR reduced tumour volumes in vivo compared with those of the control group. In conclusion, this study showed that DANCR might be an oncogenic lncRNA that regulates mTOR expression through directly binding to miR‐496. DANCR may be regarded as a biomarker or therapeutic target for ADC.

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Section: Discussionmentioning

confidence: 99%

LncRNA‐DANCR contributes to lung adenocarcinoma progression by sponging miR‐496 to modulate mTOR expression

Rui

Guo

et al. 2017

J Cellular Molecular Medi

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“…During HCC progression, abnormal chromatin marks including DNA methylation and histone modification at lncRNA genes are universally identified [74], leading to the decrease of HCC-repressive lncRNAs ( Fig. 2a) or increase of HCC-promoting lncRNAs (Fig.…”

Section: Epigenetic Modificationmentioning

confidence: 99%

“…Abnormal chromatin marks are frequently observed during HCC development largely due to dysregulation of epigenetic modifiers, including DNMTs, EZH2, HDACs, PCAF, and other effectors that regulate these epigenetic modifying enzymes [85][86][87]. Importantly, accumulating evidences have suggested that some of these epigenetic modifiers can be regulated by lncRNAs in HCC, leading to aberrant epigenetic changes such as hypomethylation, hypermethylation and other modifications [74]. For instance, UHRF1 drives HCC through inducing global DNA hypomethylation, and further study revealed that lncRNA UPAT can directly bind to UHRF1 and therefore protect it from degradation, indicating that lncRNA UPAT-mediated UHRF1 stabilization may be an oncogenic factor of HCC [88,89].…”

Section: Dna Binding and Chromatin Remodelingmentioning

confidence: 99%

The role of long noncoding RNAs in hepatocellular carcinoma

et al. 2020

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Hepatocellular carcinoma (HCC) is the most frequent subtype of primary liver cancer and one of the leading causes of cancer-related death worldwide. However, the molecular mechanisms underlying HCC pathogenesis have not been fully understood. Emerging evidences have recently suggested the crucial role of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of HCC. Various HCC-related lncRNAs have been shown to possess aberrant expression and participate in cancerous phenotypes (e.g. persistent proliferation, evading apoptosis, accelerated vessel formation and gain of invasive capability) through their binding with DNA, RNA or proteins, or encoding small peptides. Thus, a deeper understanding of lncRNA dysregulation would provide new insights into HCC pathogenesis and novel tools for the early diagnosis and treatment of HCC. In this review, we summarize the dysregulation of lncRNAs expression in HCC and their tumor suppressive or oncogenic roles during HCC tumorigenesis. Moreover, we discuss the diagnostic and therapeutic potentials of lncRNAs in HCC.

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“…DNA methylation status of RNA was closely related to the gene expression and the carcinogenesis of hepatic cancer [18,19]. Eukaryotic lncRNA also take part in the metastasis and prognosis of hepatocellular carcinoma, through regulating the chromatin remodeling and methylation [20,21].…”

Section: Discussionmentioning

confidence: 99%

Identification of lncRNA FAM99A gene as a prognostic biomarker of hepatocellular carcinoma

Sun¹,

Lv²,

Zhong³

2020

Preprint

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Background The complicated pathogenesis of hepatic cancer involves multiple clinical prognosis-associated oncogenes. Methods We utilized the bioinformatics approach to analyze the data from hepatic cancer cases collected by TCGA repository. Results We first found that the FAM99A (Family With Sequence Similarity 99 Member A) gene, a long non-coding RNA (lncRNA), is lowly expressed in hepatocellular carcinoma and closely related to clinical prognosis. We further analyzed the underling molecular mechanism from the perspectives of copy number variation (CNV), DNA methylation, immune cell infiltration, and related cellular pathway. Even though we did not observe a strong correlation between the FAM99A expression and the CNV or immune cell infiltration, the high methylation levels of the five methylated probe sites (cg24218935, cg01745044, cg04353359, cg04938738, cg25356611) were found to be negatively correlated with low expression level of FAM99A. Besides, we performed the enrichment analysis to screen out a group of FAM99A-correlated genes and molecular pathways, such as complement cascade, RNA metabolism, drug metabolic process, PPAR signaling pathway, or cell cycle. Conclusions The liver-specific FAM99A gene was first identified as a prognosis marker of hepatocellular carcinoma, and the underlying molecular mechanism involves DNA methylation and a series of cellular pathways.

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Long noncoding RNA, the methylation of genomic elements and their emerging crosstalk in hepatocellular carcinoma

Cited by 40 publications

References 77 publications

LncRNA‐DANCR contributes to lung adenocarcinoma progression by sponging miR‐496 to modulate mTOR expression

LncRNA‐DANCR contributes to lung adenocarcinoma progression by sponging miR‐496 to modulate mTOR expression

The role of long noncoding RNAs in hepatocellular carcinoma

Identification of lncRNA FAM99A gene as a prognostic biomarker of hepatocellular carcinoma

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