A novel reannotation strategy for dissecting DNA methylation patterns of human long intergenic non-coding RNAs in cancers

Zhi, Hui; Ning, Shangwei; Li, Xiang; Li, Yuyun; Wu, Wei; Li, Xia

doi:10.1093/nar/gku575

Cited by 40 publications

(39 citation statements)

References 76 publications

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“…As reported by several lncRNA profiling studies [18–20], DNA methylation in the CpG island of a lncRNA gene promoter may regulate the expression of the lncRNA gene, just like it does for coding genes. We therefore examined methylation values in the TCGA database generated from the Illumina HumanMethylation450 BeadChip, and integrated the data with gene expression results.…”

Section: Discussionmentioning

confidence: 97%

LINC00472 expression is regulated by promoter methylation and associated with disease-free survival in patients with grade 2 breast cancer

Wang

Loo

et al. 2015

Breast Cancer Res Treat

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Long non-coding RNAs (lncRNAs) are a class of newly recognized DNA transcripts that have diverse biological activities. Dysregulation of lncRNAs may be involved in many pathogenic processes including cancer. Recently, we found an intergenic lncRNA, LINC00472, whose expression was correlated with breast cancer progression and patient survival. Our findings were consistent across multiple clinical datasets and supported by results from in vitro experiments. To evaluate further the role of LINC00472 in breast cancer, we used various online databases to investigate possible mechanisms that might affect LINC00472 expression in breast cancer. We also analyzed associations of LINC00472 with estrogen receptor, tumor grade, and molecular subtypes in additional online datasets generated by microarray platforms different from the one we investigated previously. We found that LINC00472 expression in breast cancer was regulated more possibly by promoter methylation than by the alteration of gene copy number. Analysis of additional datasets confirmed our previous findings of high expression of LINC00472 associated with ER-positive and low-grade tumors and favorable molecular subtypes. Finally, in nine datasets, we examined the association of LINC00472 expression with disease-free survival in patients with grade 2 tumors. Meta-analysis of the datasets showed that LINC00472 expression in breast tumors predicted the recurrence of breast cancer in patients with grade 2 tumors. In summary, our analyses confirm that LINC00472 is functionally a tumor suppressor, and that assessing its expression in breast tumors may have clinical implications in breast cancer management.

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Section: Discussionmentioning

confidence: 97%

LINC00472 expression is regulated by promoter methylation and associated with disease-free survival in patients with grade 2 breast cancer

Wang

Loo

et al. 2015

Breast Cancer Res Treat

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“…For instance, the lncRNA MEG3, the expression of which is indirectly regulated by mir-29a in HCC cells, inhibits the activity of DNA methyltransferase and reduces MEG3 expression [43, 44]. Thus, further studies on promoter hypermethylation are required to determine the upstream regulatory mechanisms of decreased CPS1-IT expression in HCC.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA CPS1-IT1 suppresses the metastasis of hepatocellular carcinoma by regulating HIF-1α activity and inhibiting epithelial-mesenchymal transition

Wang

Lin

et al. 2016

Oncotarget

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Recently, increasing numbers of long noncoding RNAs (lncRNAs), with both oncogenic and tumor-suppressive potential, have been found to be aberrantly expressed in various human cancers. However, the function of lncRNAs in hepatocellular carcinoma (HCC) progression remains largely unknown. In this study, we performed a comprehensive microarray analysis of lncRNA expression using human HCC specimens. After validation in 119 human HCC tissues, we identified a novel tumor suppressor lncRNA, CPS1 intronic transcript 1 (CPS1-IT1). To elucidate the clinical significance of CPS1-IT1 in HCC, correlations between CPS1-IT1 levels, clinical parameters, and survival outcomes were analyzed. In vitro and in vivo functional assays were also performed to dissect the potential underlying mechanisms. Expression of CPS1-IT1 was significantly decreased in 73% of HCC tissues, and patients with low CPS1-IT1 expression had poor survival outcomes. Furthermore, in vitro functional assays indicated that CPS1-IT1 significantly reduced cell proliferation, migration and invasion capacities through reduced Hsp90 binding to and activation of HIF-1α, thereby suppressing the epithelial-mesenchymal transition (EMT). An in vivo animal model also demonstrated the tumor suppressor role of CPS1- IT1 via decreased tumor growth and metastasis. In conclusion, lncRNA CPS1-IT1 acts as a tumor suppressor in HCC by reducing HIF-1α activation and suppressing EMT. The findings of this study establish a function for CPS1-IT1 in HCC progression and suggest its potential as a new prognostic biomarker and target for HCC therapy.

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“…Moreover, patterns of lincRNA promoter methylation are associated with cancer status, subtype or prognosis. These results suggest that a large number of lncRNA genes are potential targets of aberrant DNA methylation, and they could be useful biomarkers and potential therapeutic targets [ 171 ].…”

Section: Epigenetic Dysregulation Of Lncrna Genesmentioning

confidence: 89%

“…To unravel the DNA methylation profi les of lincRNA genes in cancer, Zhi et al have re-annotated Infi nium HumanMethylation450 BeadChip array data obtained from 4629 tumor samples and 705 samples of normal tissue [ 171 ]. They have classifi ed the 2461 lincRNA genes as prone to methylation (PM) or resistant to methylation (RM) based on their promoter methylation patterns in tumors.…”

Section: Epigenetic Dysregulation Of Lncrna Genesmentioning

confidence: 99%

Relationship Between Noncoding RNA Dysregulation and Epigenetic Mechanisms in Cancer

Suzuki

Maruyama

Yamamoto

et al. 2016

Advances in Experimental Medicine and Biology

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Epigenetic alterations, including aberrant DNA methylation and histone modification, play key roles in the dysregulation of tumor-related genes, thereby affecting numerous cellular processes, including cell proliferation, cell adhesion, apoptosis, and metastasis. In recent years, studies have demonstrated that short and long noncoding RNAs (ncRNAs) are key players in the initiation and progression of cancer, and epigenetic mechanisms are deeply involved in their dysregulation. Indeed, the growing list of microRNA (miRNA) genes aberrantly methylated in cancer suggests that a large number of miRNAs act as tumor suppressors or oncogenes. In addition, emerging evidence suggests that dysregulation of long ncRNAs (lncRNAs) plays critical roles in tumorigenesis. And because ncRNAs are involved in regulating gene expression through interaction with epigenetic modifiers, their dysregulation appears causally related to epigenetic alterations in cancer. Dissection of the interrelationships between ncRNAs and epigenetic alterations has the potential to reveal novel approaches to the diagnosis and treatment of cancer.

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A novel reannotation strategy for dissecting DNA methylation patterns of human long intergenic non-coding RNAs in cancers

Cited by 40 publications

References 76 publications

LINC00472 expression is regulated by promoter methylation and associated with disease-free survival in patients with grade 2 breast cancer

LINC00472 expression is regulated by promoter methylation and associated with disease-free survival in patients with grade 2 breast cancer

Long noncoding RNA CPS1-IT1 suppresses the metastasis of hepatocellular carcinoma by regulating HIF-1α activity and inhibiting epithelial-mesenchymal transition

Relationship Between Noncoding RNA Dysregulation and Epigenetic Mechanisms in Cancer

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