DNA Methylation in Epidermal Differentiation, Aging, and Cancer

Köhler, Florian; Rodríguez-Paredes, Manuel

doi:10.1016/j.jid.2019.05.011

Cited by 61 publications

(55 citation statements)

References 136 publications

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“…Most of the genes had low methylation levels. Aberrant DNA methylation plays a crucial role in carcinogenesis [25, 26]. Therefore, we speculate that hypomethylation may be one cause of the upregulation of the 20 hub genes.…”

Section: Discussionmentioning

confidence: 99%

A twenty gene-based gene set variation score reflects the pathological progression from cirrhosis to hepatocellular carcinoma

Lin

Liang

et al. 2019

Aging

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The molecular mechanism of the pathological progression from cirrhosis to hepatocellular carcinoma (HCC) remains elusive. In the present study, tissue samples from normal liver, cirrhosis and HCC were subjected to differentially gene expression analysis, weighted gene correlation network analysis to identify the twenty hub genes (TOP2A, CDC20, PTTG1, CDCA5, CCNB2, PRC1, KIF20A, SF3B4, HSP90AB1, FOXD2, PLOD3, CCT3, SETDB1, VPS45, SPDL1, RACGAP1, MED24, KIAA0101, ZNF282, and USP21) in the pathological progression from cirrhosis to HCC. Each sample was calculated a hub gene set variation analysis (HGSVA) score using Gene Set Variation Analysis, The HGSVA score significantly increased with progression from cirrhosis to HCC, and this result was validated in two independent data sets. Moreover, this score may be used as a blood-based marker for HCC and is an independent prognostic factor of recurrence-free survival (RFS) and overall survival (OS). High expression of the hub genes may be driven by hypomethylation. The twenty gene-based gene set variation score may reflect the pathological progression from cirrhosis to HCC and is an independent prognostic factor for both OS and RFS.

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Section: Discussionmentioning

confidence: 99%

A twenty gene-based gene set variation score reflects the pathological progression from cirrhosis to hepatocellular carcinoma

Lin

Liang

et al. 2019

Aging

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“…Global DNA hypomethylation and differential promoter methylation are major characteristics of tumorigenesis. Global hypomethylation of the entire genome in peripheral blood leukocytes is demonstrated as the risk factor for colorectal and breast cancer [[10], [11], [12], [13]]. DNA hypomethylation on the promoter region was linked to increased expression of cyclin D2 and maspin in gastric carcinoma and elevated carbonic anhydrase family gene in human renal-cell carcinoma [[14], [15], [16]].…”

Section: Introductionmentioning

confidence: 99%

Homocysteine-methionine cycle is a metabolic sensor system controlling methylation-regulated pathological signaling

et al. 2020

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Homocysteine-Methionine (HM) cycle produces universal methyl group donor S-adenosylmethione (SAM), methyltransferase inhibitor S-adenosylhomocysteine (SAH) and homocysteine (Hcy). Hyperhomocysteinemia (HHcy) is established as an independent risk factor for cardiovascular disease (CVD) and other degenerative disease.We selected 115 genes in the extended HM cycle (31 metabolic enzymes and 84 methyltransferases), examined their protein subcellular location/partner protein, investigated their mRNA levels and mapped their corresponding histone methylation status in 35 disease conditions via mining a set of public databases and intensive literature research. We have 6 major findings. 1) All HM metabolic enzymes are located only in the cytosol except for cystathionine-β-synthase (CBS), which was identified in both cytosol and nucleus. 2) Eight disease conditions encountered only histone hypomethylation on 8 histone residues (H3R2/K4/R8/K9/K27/K36/K79 and H4R3). Nine disease conditions had only histone hypermethylation on 8 histone residues (H3R2/K4/K9/K27/K36/K79 and H4R3/K20). 3) We classified 9 disease types with differential HM cycle expression pattern. Eleven disease conditions presented most 4 HM cycle pathway suppression. 4) Three disease conditions had all 4 HM cycle pathway suppression and only histone hypomethylation on H3R2/K4/R8/K9/K36 and H4R3. 5) Eleven HM cycle metabolic enzymes interact with 955 proteins. 6) Five paired HM cycle proteins interact with each other.We conclude that HM cycle is a key metabolic sensor system which mediates receptor-independent metabolism-associated danger signal recognition and modulates SAM/SAH-dependent methylation in disease conditions and that hypomethylation on frequently modified histone residues is a key mechanism for metabolic disorders, autoimmune disease and CVD. We propose that HM metabolism takes place in the cytosol, that nuclear methylation equilibration requires a nuclear-cytosol transfer of SAM/SAH/Hcy, and that Hcy clearance is essential for genetic protection.

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“…A previous study has shown that altered circadian regulation in cancer stem cells may contribute to disease progression (9). Endogenous circadian rhythms are maintained by two feedback loops.…”

Section: Introductionmentioning

confidence: 99%

“…Endogenous circadian rhythms are maintained by two feedback loops. Clock circadian regulator (CLOCK) and brain and muscle Arnt-like protein-1 (BMAL1) form heterodimers to rhythmically activate the expression of transcriptional repressor proteins, such as period 1/2/3 and cryptochrome 1/2, which form a complex to inhibit CLOCK and BMAL1 transcriptional activity (9)(10)(11). In some types of cancer and model systems, period circadian clock 2 (PER2) serves as a tumor suppressor gene.…”

Section: Introductionmentioning

confidence: 99%

PER2 inhibits proliferation and stemness of glioma stem cells via the Wnt/β‑catenin signaling pathway

Hou

Xia

et al. 2020

Oncol Rep

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Glioblastoma is a highly malignant tumor that contains stem-like cells known as glioma stem cells (GSCs), which lare associated with an increased risk of glioma occurrence, recurrence and poor prognosis. Circadian clock gene, period circadian clock 2 (PER2) expression has been revealed to be inhibited in various types of cancer. However, the precise role and potential mechanisms of PER2 in GSCs remains unclear. The present study demonstrated that PER2 mRNA and protein expression was downregulated in GSCs compared with non-stem glioma cells, which indicated that PER2 could be involved in the malignant process of glioma. Furthermore, functional studies revealed that PER2 overexpression could induce GSC arrest at the G0/G1 phase and suppress their proliferation, stemness and invasion ability in vitro and in vivo. Subsequently, the Wnt/β-catenin signaling pathway was identified as the target of PER2 in GSCs. These results indicated that PER2 plays a critical role in regulating the stemness of GSCs and provides a novel therapeutic target to overcome the effects of GSCs.

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DNA Methylation in Epidermal Differentiation, Aging, and Cancer

Cited by 61 publications

References 136 publications

A twenty gene-based gene set variation score reflects the pathological progression from cirrhosis to hepatocellular carcinoma

A twenty gene-based gene set variation score reflects the pathological progression from cirrhosis to hepatocellular carcinoma

Homocysteine-methionine cycle is a metabolic sensor system controlling methylation-regulated pathological signaling

PER2 inhibits proliferation and stemness of glioma stem cells via the Wnt/β‑catenin signaling pathway

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