Estrogen-regulated PTTG1 promotes breast cancer progression by regulating cyclin kinase expression

Meng, Chun-hui; Zou, Yan; Hong, Wan; Bao, Chunhua; Jia, Xin

doi:10.1186/s10020-020-00161-7

Cited by 27 publications

(22 citation statements)

References 28 publications

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“…A previous study reported that PTTG1, an overexpressed gene in seminoma tumor, promoted the migration and invasion of tumor cells via activation of MMP-2 [ 25 ]. In addition, the prognostic values of PTTG1 were also reported in several tumors, such as breast carcinoma and prostate carcinoma [ 8 , 26 ]. According to the findings above, PTTG1 is an oncogene in the above tumors.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of PTTG1 and Its Methylation in Lung Adenocarcinoma

Bai

Liang

et al. 2022

Journal of Oncology

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Pituitary tumor-transforming gene-1 (PTTG1), one type of DNA repair-related gene, has been reported to be dysregulated in several tumors and serve as a tumor promotor. Previously, the oncogenic roles of PTTG1 were also reported in lung adenocarcinoma (LUAD). However, the prognostic values of PTTG1 in LUAD and the possible mechanism of its dysregulation have not been clarified. We analyzed TCGA datasets and reported that PTTG1 expression showed a distinct increase within LUAD specimens in comparison with nontumor specimens. Further survival study revealed that patients containing a great PTTG1 level had noticeably less overall survival and progression-free survival as compared with patients containing a low PTTG1 level. Multivariate analyses confirmed that PTTG1 expression was a factor of prognosis that is independent in terms of LUAD patients. Besides, PTTG1 methylation had a negative regulation on PTTG1, so PTTG1 had a high expressing level in LUAD tissues. However, the relation between hypermethylation and overall survival was not demonstrated using TCGA datasets. In addition, we observed that LUAD specimens with advanced stages exhibited a higher level of PTTG1. Finally, the dysregulated genes related to PTTG1 expression were screened, and KEGG assays revealed that the above genes were involved in the p53 signaling pathway, indicating the possible regulatory function of PTTG1 in the p53 signaling pathway. Overall, our findings suggest that PTTG1 may serve as an efficient clinical biomarker and a therapeutic target for patients suffering from LUAD.

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Section: Discussionmentioning

confidence: 99%

Prognostic Significance of PTTG1 and Its Methylation in Lung Adenocarcinoma

Bai

Liang

et al. 2022

Journal of Oncology

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“…Acid ceramidase (ASAH1) can upregulated the CCNB2 expression and promote BC cell proliferation [46]. Meng et al reported that PTTG1 was overexpressed in BC and might target CCNB2, resulting in more BC cells distributed in S phase [47]. To date, there is no report revealing the expression level of CCNB3 in BC and predicting the prognostic value for BC patients.…”

Section: Discussionmentioning

confidence: 99%

Systematic Analyses of the Expression, Function, and Prognostic Value of CCNBs in Breast Caner

Liu

Yu-qi

Wang

et al. 2021

Preprint

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Background Cyclin B (CCNB) family plays key roles in the cell cycle, cell division and proliferation. Three members of CCNB family have been identified, including CCNB1, CCNB2 and CCNB3. Many studies have explored the roles of CCNBs in the tumorigenesis and pathogenesis of different types of cancer. However, the expression level, function, and prognostic value of CCNBs in breast caner (BC) are still unclear.Methods We explored the specific alterations of CCNBs in BC and predicted their prognostic value for BC patients. Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, STRING, Database for Annotation,Visualization and Integrated Discovery (DAVID) databases were used for above analyses.Results We found that CCNB1 amd CCNB2 were significantly overexpressed in BC compared with normal samples, but not CCNB3. Survival analysis showed that upregulated CCNB1 and CCNB2 expression levels were associated with poor prognosis of BC patients, while high CCNB3 expression was related to good prognosis for BC patients. Furthermore, gene oncology (GO) enrichment analysis was performed to reveal the functions of CCNBs and the interacted genes related to CCNBs. In addition, hsa-miR-139-5p and has-miR-944 were identified to be potentially involved in the regulation of CCNB1.Conclusion Our study suggests that CCNB1, CCNB2 are potential targets of precise therapy for BC patients and that CCNB3 is a novel biomarker for the good prognosis of BC patients.

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“…For example, PTTG1 has been implicated in breast cancer development through regulation of the epithelial-mesenchymal transition (EMT) and functions of p27 and RhoA signaling ( Quereda and Malumbres, 2009 ; Yoon et al, 2012 ; Lim et al, 2016 ). In addition, estrogen has been shown to promote breast cancer development through increasing PTTG1 expression ( Chen et al, 2017 ; Meng et al, 2020 ). Although many studies have demonstrated the roles of overexpressing PTTG1 in breast cancer metastasis, the mechanisms underlying regulation of PTTG1 expression are still unclear.…”

Section: Discussionmentioning

confidence: 99%

Simvastatin Suppresses Human Breast Cancer Cell Invasion by Decreasing the Expression of Pituitary Tumor-Transforming Gene 1

Yin

et al. 2020

Front. Pharmacol.

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Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, have been widely used to lower cholesterol and prevent cardiovascular diseases. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer, while the underlying mechanisms remain to be elucidated. Herein, we sought to investigate the effect of statins on the expression of pituitary tumor-transforming gene 1 (PTTG1), a critical gene involved in human breast cancer invasion and metastasis. Our results showed that PTTG1 is highly expressed in malignant Hs578T and MDA-MB-231 breast cancer cell lines as compared with normal or less malignant breast cancer cells. Furthermore, we found that the expression of PTTG1 was markedly suppressed by lipophilic statins, such as simvastatin, fluvastatin, mevastatin, and lovastatin, but not by hydrophilic pravastatin. In a dose and time dependent manner, simvastatin suppressed PTTG1 expression by decreasing PTTG1 mRNA stability in MDA-MB-231 cells. Both siRNA-mediated knockdown of PTTG1 expression and simvastatin treatment markedly inhibited MDA-MB-231 cell invasion, MMP-2 and MMP-9 activity, and the expression of PTTG1 downstream target genes, while ectopic expression of PTTG1 promoted cancer cell invasion, and partly reversed simvastatin-mediated inhibition of cell invasion. Mechanistically, we found that inhibition of PTTG1 expression by simvastatin was reversed by geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate, suggesting the involvement of geranylgeranyl synthesis in regulating PTTG1 expression. Our results identified statins as novel inhibitors of PTTG1 expression in breast cancer cells and provide mechanistic insights into how simvastatin prevent breast cancer metastasis as observed in recent preclinical and clinical studies.

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Estrogen-regulated PTTG1 promotes breast cancer progression by regulating cyclin kinase expression

Cited by 27 publications

References 28 publications

Prognostic Significance of PTTG1 and Its Methylation in Lung Adenocarcinoma

Prognostic Significance of PTTG1 and Its Methylation in Lung Adenocarcinoma

Systematic Analyses of the Expression, Function, and Prognostic Value of CCNBs in Breast Caner

Simvastatin Suppresses Human Breast Cancer Cell Invasion by Decreasing the Expression of Pituitary Tumor-Transforming Gene 1

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