Epigenetic marks responsible for cadmium-induced melanoma cell overgrowth

Venza, Mario; Visalli, Maria; Biondo, Carmelo; Oteri, Rosaria; Agliano, Federica; Morabito, Silvia; Teti, Diana

doi:10.1016/j.tiv.2014.10.020

Cited by 35 publications

(24 citation statements)

References 57 publications

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“…p16 INK4A regulates the cell cycle through the inhibition of CDK4 and CDK6 by cyclin D1 (CCND1), and its inactivation results in the hyperphosphorylation of RB1 with unlimited cell cycle progression [13]. Hypermethylation of p16 INK4A is the most relevant factor in the promotion of melanoma cell growth induced by cadmium and suppression of the cell apoptosis pathway [14]. In addition, p14…”

Section: Introductionmentioning

confidence: 99%

Effects of CDKN2A (p16INK4A/p14ARF) Over-Expression on Proliferation and Migration of Human Melanoma A375 Cells

Bai

Yu²,

Long³

et al. 2016

Cell Physiol Biochem

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Objective: This study aims to investigate the effects of CDKN2A (p16^INK4A/p14^ARF) over-expression on the proliferation and migration of human melanoma A375 cells. Methods: Melanoma tissues and pigmented nevi tissues were collected. Human melanoma A375 cells were transfected by CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) over-expressing vectors and then assigned into blank, negative control (NC), p16^INK4A and p14^ARF groups. The expression of CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) mRNA and protein was detected by qRT-PCR and Western blotting. CCK-8, flow cytometry and Transwell assays were applied to observe cell proliferation, the cell cycle and apoptosis, and migration and invasion, respectively. The model of subcutaneous xenografts in nude mice was established to measure cell growth in vivo. Results: Compared with pigmented nevi tissues, CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) mRNA and protein expression were significantly decreased in melanoma tissues. CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) over-expression inhibited proliferation, migration, invasion and progression from G0/G1 to S phase of A375 cells and xenograft tumor growth, but promoted apoptosis. Conclusion: Our study demonstrated that over-expression of CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) suppressed proliferation and migration of human melanoma A375 cells.

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Section: Introductionmentioning

confidence: 99%

Effects of CDKN2A (p16INK4A/p14ARF) Over-Expression on Proliferation and Migration of Human Melanoma A375 Cells

Bai

Yu²,

Long³

et al. 2016

Cell Physiol Biochem

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“…Beside genetic alterations in cancer cells, epigenetic changes (DNA methylation and histone modifications) can also induce silencing of tumor suppressor genes allowing cancer cells to escape apoptosis and promote tumor progression [1–4]. The epigenetic reader UHRF1 (U biquitin-like, containing P H D and R ING F inger domains 1) , an oncogene overexpressed in various human cancer cells is one of the major players involved in apoptosis inhibition by inducing epigenetic silencing of TSGs [5–8].…”

Section: Introductionmentioning

confidence: 99%

Signalling pathways in UHRF1-dependent regulation of tumor suppressor genes in cancer

Alhosin

Omran

Zamzami

et al. 2016

J Exp Clin Cancer Res

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Epigenetic silencing of tumor suppressor genes (TSGs) through DNA methylation and histone changes is a main hallmark of cancer. Ubiquitin-like with PHD and RING Finger domains 1 (UHRF1) is a potent oncogene overexpressed in various solid and haematological tumors and its high expression levels are associated with decreased expression of several TSGs including p16 INK4A, BRCA1, PPARG and KiSS1. Using its several functional domains, UHRF1 creates a strong coordinated dialogue between DNA methylation and histone post-translation modification changes causing the epigenetic silencing of TSGs which allows cancer cells to escape apoptosis. To ensure the silencing of TSGs during cell division, UHRF1 recruits several enzymes including histone deacetylase 1 (HDAC1), DNA methyltransferase 1 (DNMT1) and histone lysine methyltransferases G9a and Suv39H1 to the right place at the right moment. Several in vitro and in vivo works have reported the direct implication of the epigenetic player UHRF1 in tumorigenesis through the repression of TSGs expression and suggested UHRF1 as a promising target for cancer treatment. This review describes the molecular mechanisms underlying UHRF1 regulation in cancer and discusses its importance as a therapeutic target to induce the reactivation of TSGs and subsequent apoptosis.

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“…DNA hypomethylation has been suggested to have potential utility for cancer classification and prediction of clinical course [46]. Selective hypermethylation at the promoters of a number of tumor suppressor genes have been well-documented melanoma (Table 1) [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66].…”

Section: Dna Methylationmentioning

confidence: 99%

“…APC Diagnostic/prognostic marker; therapeutic target APC gene promoter hypermethylation in melanoma cell lines and patient melanoma tissue samples; leads to APC's transcriptional silencing which in turn increases cell proliferation without compromising invasiveness; associated with poor prognosis [51] ASC/PYCARD Therapeutic target Plays stage-dependent role in tumorigenesis by differential regulation of NF-κB and IL-1β [52] p16(INK4A)/Caspase-8 Methylation and silencing in cutaneous melanoma is induced by Cadmium and results in resistance to apoptosis [53] CDH1 Prognostic marker Inversely correlated with melanoma stage and Breslow thickness, higher expression is associated with favorable prognosis [57] CDKN2A Diagnostic marker; therapeutic target Major high-risk melanoma susceptibility gene; tumor-suppressor capable of blocking cell cycle at the G1-S checkpoint and activating RB [54] FRZB Inhibits melanoma migration and invasion via Wnt5a signaling; part of multilocus DNA-methylation signature that discriminates melanomas from nevi [55] LXN Densely methylated in melanoma cell lines and tumors; increased expression inhibits proliferation and alters stem cell-like properties [58,59] PTEN Prognostic marker, therapeutic target Tumor suppressor, the silencing of which results in activation of the AKT pathway and thereby promotes melanoma growth, proliferation, and development; hypermethylated PTEN is found in blood of patients bearing metastatic melanoma and is associated with poor survival; PTEN loss also correlates with BRAF activation [60][61][62] RAR-b2 Diagnostic marker, therapeutic target Methylated in human melanoma cell lines and clinical specimens; RAR-b2 can be reactivated by 5-aza 2′-deoxycytidine to inhibit cell growth through the regulation of ATRA [63] RASSF1A Staging and prognostic marker; therapeutic target Degree of methylation varies with tumor stage; silencing leads to suppression of mitochondrion-dependent apoptosis [64] SOCS1 Staging marker; therapeutic target Hypermethylation increases with advancing clinical tumor stage; overexpression inhibits proliferation by causing G1/S blockage [65,66] TFAP2A Therapeutic target Down-regulated in melanomas compared with nevi; epigenetically silenced in advanced melanoma [67] Hypomethylated genes…”

Section: Hypermethylated Genesmentioning

confidence: 99%

Epigenetic Markers in Melanoma

Guo

Lee

et al. 2015

Melanoma Manag.

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Melanoma, one of the most virulent forms of human malignancy, is the primary cause of mortality from cancers arising from the skin. The prognosis of metastatic melanoma remains dismal despite targeted therapeutic regimens that exploit our growing understanding of cancer immunology and genetic mutations that drive oncogenic cell signaling pathways in cancer. Epigenetic mechanisms, including DNA methylation/demethylation, histone modifications and noncoding RNAs recently have been shown to play critical roles in melanoma pathogenesis. Current evidence indicates that imbalance of DNA methylation and demethylation, dysregulation of histone modification and chromatin remodeling, and altered translational control by noncoding RNAs contribute to melanoma tumorigenesis. Here, we summarize the most recent insights relating to epigenetic markers, focusing on diagnostic potential as well as novel therapeutic approaches for more effective treatment of advanced melanoma.

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Epigenetic marks responsible for cadmium-induced melanoma cell overgrowth

Cited by 35 publications

References 57 publications

Effects of CDKN2A (p16INK4A/p14ARF) Over-Expression on Proliferation and Migration of Human Melanoma A375 Cells

Effects of CDKN2A (p16INK4A/p14ARF) Over-Expression on Proliferation and Migration of Human Melanoma A375 Cells

Signalling pathways in UHRF1-dependent regulation of tumor suppressor genes in cancer

Epigenetic Markers in Melanoma

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