Methylation alterations are not a major cause of PTTG1 missregulation

Hidalgo, Manuel; Sáez, Carmen; Ferrero, Eduardo; Castilla, Carolina; Ramírez-Lorca, Reposo; Peláez, Pablo; Ruiz, Agustı́n; Japón, Miguel Á.; Royo, José Luis

doi:10.1186/1471-2407-8-110

Cited by 5 publications

(8 citation statements)

References 25 publications

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“…Epigenetic studies using prostate cancer cell lines suggest that neither methylation status nor loss of heterozygosity is responsible for the altered expression of PTTG1 in tumours (Ref. 51). Histone acetylation modification has recently been implicated in PTTG1 regulation.…”

Section: Regulation Of Pttg Expressionmentioning

confidence: 99%

Pituitary tumor-transforming gene and its binding factor in endocrine cancer

Smith

Franklyn

McCabe

2010

Expert Rev. Mol. Med.

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The pituitary tumor-transforming gene (PTTG1) encodes a multifunctional protein (PTTG) that is overexpressed in numerous tumours, including pituitary, thyroid, breast and ovarian carcinomas. PTTG induces cellular transformation in vitro and tumourigenesis in vivo, and several mechanisms by which PTTG contributes to tumourigenesis have been investigated. Also known as the human securin, PTTG is involved in cell cycle regulation, controlling the segregation of sister chromatids during mitosis. This review outlines current information regarding PTTG structure, expression, regulation and function in the pathogenesis of neoplasia. Recent progress concerning the use of PTTG as a prognostic marker or therapeutic target will be considered. In addition, the PTTG binding factor (PBF), identified through its interaction with PTTG, has also been established as a proto-oncogene that is upregulated in several cancers. Current knowledge regarding PBF is outlined and its role both independently and alongside PTTG in endocrine and related cancers is discussed.

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Section: Regulation Of Pttg Expressionmentioning

confidence: 99%

Pituitary tumor-transforming gene and its binding factor in endocrine cancer

Smith

Franklyn

McCabe

2010

Expert Rev. Mol. Med.

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Section: Discussionmentioning

confidence: 99%

“…Sequencing scan in sixteen human pituitary adenoma biopsies failed to identify any promoter mutation of the Securin gene and therefore it is believed that promoter mutation does not play any role for its enhanced expression [38,39]. Further, no loss of heterozygosity has been reported for the region mapping the PTTG1/Securin locus [39]. In a separate study, it was demonstrated that RAN-alkaloids create more relaxed chromatin structure by altering poly-ADP-ribosylation of cellular proteins which could be considered as a causative factor for RAN-induced carcinogenesis [40].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we have analysed the histone covalent modi cations pattern both at the global level and in the promoter region of the Securin gene because such modi cations do have profound effects on gene promoter activity and have been extensively linked to cancer [41]. The methylation status in a CpG island at the proximal promoter region of the PTTG1/Securin gene was not evaluated since no methylation was observed in both healthy tissues and differentiated thyroid carcinoma samples, and also in prostate cancer cell lines regardless the expression status of PTTG1/Securin gene [39].…”

Section: Discussionmentioning

confidence: 99%

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Securin overexpression correlates with the activated Rb/E2F1 pathway and Histone H3 epigenetic modifications in raw areca-nut induced carcinogenesis in mice

Boruah

Singh

Swargiary

et al. 2021

Preprint

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Background Raw areca-nut (RAN) consumption induces oral, esophageal and gastric cancers which are significantly associated with the overexpression of pituitary tumor transforming gene1/Securin and chromosomal instability (CIN). Since the molecular mechanism underlying Securin upregulation remains unclear, this study is intended to investigate the association of Securin upregulation with Rb-E2F1 circuit and epigenetic histone (H3) modifications pattern both globally and in the promoter region of Securin gene. Methods Six groups of mice were used and in the treated group each mouse consumed 1 mg of RAN-extract with lime per day ad libitum in the drinking water for 60 days after which the dose was increased by 1 mg after every 60 days. Histopathological evaluation of stomach tissues was done and Securin expression was analysed by immunoblotting as well as by immunohistochemistry. ChIP-qPCR assay was performed for evaluating the recruitment of different histone modifications in the two regions of Securin promoter. Results All mice developed gastric cancer with Securin overexpression after 300 days of feeding. Immunohistochemistry data revealed hyperphosphorylation of Rb and upregulation of E2F1 in the RAN-treated samples. Increased trimethylation of H3 Lysine4 and acetylation of H3 Lysine9 and 18 both globally and in the promoter region of Securin gene was observed by increasing the level of lysine-N-methyltransferase2A, lysine-acetyltransferase, EP-300 and PCAF after RAN-treatment. ChIP-qPCR data show an increased recruitment of H3K4me3, H3K9ac and H3K18ac in the promoter of Securin gene after RAN-exposure Conclusions In light of the present results, it seems that RAN-mediated pRb-inactivation induced Securin upregulation, a putative E2F1 target, by inducing misregulation in chromatin remodeling in its promoter region which led to transcriptional activation and subsequently develop chromosomal instability. Therefore, the present results have led to the hypothesis that RAN-induced changes in the epigenetic landscape, Securin overexpression and subsequent elevation of chromosomal instability are probably a by-product of the inactivation of the pRb pathway.

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“…However, Kanakis D et al [ 20 ] failed to find any mutations in the main promoter region of PTTG1 which may result in the overexpression of the PTTG1. Another study on the genetic changes of PTTG1 also excluded methylation and LOH as causes of PTTG1 aberration in human cancers [ 21 ]. miRNAs are small non-coding RNA which participate in a wide array of cellular processes [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

PTTG1 regulated by miR-146a-3p promotes bladder cancer migration, invasion, metastasis and growth

Wei

Huang

et al. 2016

Oncotarget

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Pituitary tumor-transforming gene 1 (PTTG1) is identified as an oncogene, and overexpresses in many tumors. However, the role of PTTG1 in bladder cancer (BC) hasn't yet been characterized well. In this study, we showed the expression of PTTG1 mRNA and protein were both significantly increased in BC tissues and cells. The PTTG1 protein levels were positive correlated with increased tumor size, tumor–node–metastasis (TNM) stage, lymphatic invasion and distant metastasis of BC. PTTG1 knockdown dramatically suppressed the migration, invasion, metastasis and growth, and induced senescence and cell-cycle arrest at G0/G1 phase of BC cells. We further identified PTTG1 was the direct target of miR-146a-3p through using target prediction algorithms and luciferase reporter assay. miR-146a-3p was low expressed and negatively correlated with PTTG1 levels in BC tissues and cells. miR-146a-3p overexpression inhibited migration, invasion, metastasis and growth, and induced senescence of BC cells. Rescue experiment suggested ectopic expression of miR-146a-3p and PTTG1 suppressed migration, invasion and induced cell cycle arrest and senescence of BC cells compared to PTTG1 overexpression, confirming miR-146a-3p inhibited BC progression by targeting PTTG1. In summary, our study found miR-146a-3p/PTTG1 axis regulated BC migration, invasion, metastasis and growth, and might be a targets for BC therapy.

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Methylation alterations are not a major cause of PTTG1 missregulation

Cited by 5 publications

References 25 publications

Pituitary tumor-transforming gene and its binding factor in endocrine cancer

Pituitary tumor-transforming gene and its binding factor in endocrine cancer

Securin overexpression correlates with the activated Rb/E2F1 pathway and Histone H3 epigenetic modifications in raw areca-nut induced carcinogenesis in mice

PTTG1 regulated by miR-146a-3p promotes bladder cancer migration, invasion, metastasis and growth

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