scholarly journals Erratum: Corrigendum: Epigenetic inactivation of the CpG demethylase TET1 as a DNA methylation feedback loop in human cancers

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Lili Li ◽  
Chen Li ◽  
Haitao Mao ◽  
Zhenfang Du ◽  
Wai Yee Chan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Feedback Loop ◽  
Epigenetic Inactivation ◽  
Human Cancers

DNA methylation of mobile genetic elements in human cancers

2013 ◽  
Vol 35 (3) ◽  
pp. 265-271 ◽  
Author(s):  
Kyudong Han ◽  
Jungname Lee ◽  
Heui-Soo Km ◽  
Kwangmo Yang ◽  
Joo Mi Yi
Keyword(s):  
Dna Methylation ◽  
Mobile Genetic Elements ◽  
Genetic Elements ◽  
Human Cancers

scholarly journals The Establishment of CDK9/ RNA PolII/H3K4me3/DNA Methylation Feedback Promotes HOTAIR Expression by RNA Elongation Enhancement in Cancer

2019 ◽  
Author(s):  
Chi Hin Wong ◽  
Chi Han Li ◽  
Qifang He ◽  
Joanna Hung Man Tong ◽  
Ka-Fai To ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cancer Progression ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Transcription Elongation ◽  
Underlying Mechanism ◽  
Transcriptional Elongation ◽  
Gene Body ◽  
Gene Body Methylation ◽  
Positive Feedback Loop

SUMMARYLong non-coding RNA HOX Transcript Antisense RNA (HOTAIR) is overexpressed in multiple cancers with diverse genetic profiles, which heavily contributed to cancer progression. However, the underlying mechanism leading to HOTAIR deregulation is largely unexplored. Here, we revealed that gene body methylation promoted HOTAIR expression through enhancing the transcription elongation process in cancer. We linked up the aberrant gene body histone and DNA methylation in promoting transcription elongation via phosphorylation of Polymerase II Ser 2 by CDK7-CDK9, and elucidated the mechanism of a positive feedback loop involving CDK7, MLL1 and DNMT3A in promoting gene body methylation and overexpressing HOTAIR. To our knowledge, this is the first time to demonstrate that a positive feedback loop that involved CDK9-mediated phosphorylation of PolII and histone and gene body methylation induced robust transcriptional elongation, which heavily contributed to the upregulation of oncogenic lncRNA in cancer.

scholarly journals A Pan-Cancer Analysis of SMARCA4 Alterations in Human Cancers

2021 ◽  
Vol 12 ◽  
Author(s):  
Ling Peng ◽  
Jisheng Li ◽  
Jie Wu ◽  
Bin Xu ◽  
Zhiqiang Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Immunity ◽  
Immune Cell ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Poor Overall Survival ◽  
Atpase Subunit ◽  
Human Cancers ◽  
Cancer Types

BackgroundSMARCA4, the essential ATPase subunit of SWI/SNF chromatin remodeling complex, regulates transcription through the control of chromatin structure and is increasingly thought to play significant roles in human cancers. This study aims to explore the potential role of SMARCA4 with a view to providing insights on pathologic mechanisms implicated here.MethodsThe potential roles of SMARCA4 in different tumors were explored based on The Cancer Genome Atlas (TCGA), Genotype-tissue expression (GTEx), Tumor Immune Estimation Resource (TIMER), and Gene Set Enrichment Analysis (GSEA) datasets. The expression difference, mutation and phosphorylation status, survival, pathological stage, DNA methylation, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), tumor microenvironment (TME), and immune cell infiltration related to SMARCA4 were analyzed.ResultsHigh expression levels of SMARCA4 were observed in most cancer types. SMARCA4 expression in tumor samples correlates with poor overall survival in several cancers. Lung adenocarcinoma cases with altered SMARCA4 showed a poorer prognosis. Enhanced phosphorylation levels of S613, S695, S699, and S1417 were observed in several tumors, including breast cancer. SMARCA4 correlated with tumor immunity and associated with different immune cells and genes in different cancer types. TMB, MSI, MMR, and DNA methylation correlated with SMARCA4 dysregulation in cancers. SMARCA4 expression was negatively associated with CD8+ T-cell infiltration in several tumors. Furthermore, the SWI/SNF superfamily-type complex and ATPase complex may be involved in the functional mechanisms of SMARCA4, albeit these data require further confirmation.ConclusionsOur study offers a comprehensive understanding of the oncogenic roles of SMARCA4 across different tumors. SMARCA4 may correlate with tumor immunity.

Induction of an aggressive phenotype and poor survival in early-stage lung adenocarcinoma and epigenetic inactivation of microRNA-34b/c.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11056-11056
Author(s):  
Ernest Nadal ◽  
Marc Gallegos ◽  
Guoan Chen ◽  
Ramon Palmero ◽  
Gabriel Capella ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lung Adenocarcinoma ◽  
Prognostic Marker ◽  
Cell Lines ◽  
Early Stage ◽  
Migration And Invasion ◽  
Primary Tumors ◽  
Epigenetic Inactivation ◽  
Aggressive Phenotype ◽  
Independent Prognostic Marker

11056 Background: The microRNA-34b/c (miR-34b/c) is a transcriptional target of TP53 that is frequently mutated in primary lung adenocarcinoma (AC). We investigated the clinical implications of miR-34b/c methylation in early stage lung AC patients and the functional role of miR-34b/c re-expression in lung AC cell lines. Methods: DNA methylation of miR-34b/c promoter was assessed by real-time PCR temperature dissociation in 15 lung AC cell lines and 140 early stage lung AC resected at the Bellvitge Hospital (Barcelona) and at the University of Michigan (Ann Arbor). Patient characteristics: 65% males, 88% smokers, 68.5% stage I and 31.5% stage II. Expression of miR-34b/c was determined by TaqMan RT-PCR. Two lung AC cell lines (NCI-H1838 and SK-LU-1) were transfected with an expression vector containing both miRs and the effects upon cell proliferation, migration and invasion were determined. Results: MiR-34b/c was methylated in 40% of cell lines and in 46% of primary tumors with significant association with higher tumor stage (P=0.033), recurrence (P=0.017) and death (P=0.005). In the training set (n=58), patients with higher levels of miR-34b/c methylation had significantly shorter median DFS (28.5 months) compared to low to medium levels (not reached, log-rank P=0.016). In the test set (n=82), higher levels of miR-34b/c methylation were also associated to shorter median DFS (19 months) compared to patients with low to medium levels (not reached, log-rank P=0.005). MiR-34b/c methylation remained an independent prognostic marker for DFS after adjusting by age, gender and stage. Tumors harboring TP53 mutations and miR-34b/c methylation expressed significantly lower levels of miR-34b/c (P≤0.001). Stable cells expressing miR-34b/c had lower proliferation rate relative to cells transfected with empty vector (P≤0.001). Expressing miR-34b/c in SK-LU-1 cells reduced migration and invasion ability. Conclusions: Epigenetic inactivation of miR-34b/c by DNA methylation is an independent prognostic marker in early stage lung AC. Ectopic expression of miR-34b/c generated a less aggressive phenotype in lung AC cell lines suggesting a potential for therapeutic targeting.

MicroRNAs miR-199a-5p and -3p Target the Brm Subunit of SWI/SNF to Generate a Double-Negative Feedback Loop in a Variety of Human Cancers

2010 ◽  
Vol 71 (5) ◽  
pp. 1680-1689 ◽  
Author(s):  
Kouhei Sakurai ◽  
Chihiro Furukawa ◽  
Takeshi Haraguchi ◽  
Ken-ichi Inada ◽  
Kazuya Shiogama ◽  
...  
Keyword(s):  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
Double Negative ◽  
Human Cancers

scholarly journals Global impact of somatic structural variation on the DNA methylome of human cancers

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yiqun Zhang ◽  
Lixing Yang ◽  
Melanie Kucherlapati ◽  
Angela Hadjipanayis ◽  
Angeliki Pantazi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Copy Number ◽  
Structural Variation ◽  
Immune Cell ◽  
Cpg Islands ◽  
Dna Methyltransferases ◽  
Altered Expression ◽  
Dna Methylome ◽  
Human Cancers ◽  
Analytical Approaches

Abstract Background Genomic rearrangements exert a heavy influence on the molecular landscape of cancer. New analytical approaches integrating somatic structural variants (SSVs) with altered gene features represent a framework by which we can assign global significance to a core set of genes, analogous to established methods that identify genes non-randomly targeted by somatic mutation or copy number alteration. While recent studies have defined broad patterns of association involving gene transcription and nearby SSV breakpoints, global alterations in DNA methylation in the context of SSVs remain largely unexplored. Results By data integration of whole genome sequencing, RNA sequencing, and DNA methylation arrays from more than 1400 human cancers, we identify hundreds of genes and associated CpG islands (CGIs) for which the nearby presence of a somatic structural variant (SSV) breakpoint is recurrently associated with altered expression or DNA methylation, respectively, independently of copy number alterations. CGIs with SSV-associated increased methylation are predominantly promoter-associated, while CGIs with SSV-associated decreased methylation are enriched for gene body CGIs. Rearrangement of genomic regions normally having higher or lower methylation is often involved in SSV-associated CGI methylation alterations. Across cancers, the overall structural variation burden is associated with a global decrease in methylation, increased expression in methyltransferase genes and DNA damage response genes, and decreased immune cell infiltration. Conclusion Genomic rearrangement appears to have a major role in shaping the cancer DNA methylome, to be considered alongside commonly accepted mechanisms including histone modifications and disruption of DNA methyltransferases.

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