<i>MTSS1</i> hypermethylation is associated with prostate cancer progression

Chen, Junjie; Huang, Liang; Zhu, Quan; Wang, Zhao

doi:10.1002/jcp.29172

Cited by 11 publications

(8 citation statements)

References 39 publications

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“…Our results also shed light on chromosome 8q24 genes that, despite their amplification, are profoundly repressed in PCa, such as MTSS1. This observation is in line with the documented epigenetic repression of this gene through different molecular means [72,73].…”

Section: Discussionsupporting

confidence: 89%

Genomic and Functional Regulation of TRIB1 Contributes to Prostate Cancer Pathogenesis

Shahrouzi

Astobiza

Cortazar

et al. 2020

Cancers

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Prostate cancer is the most frequent malignancy in European men and the second worldwide. One of the major oncogenic events in this disease includes amplification of the transcription factor cMYC. Amplification of this oncogene in chromosome 8q24 occurs concomitantly with the copy number increase in a subset of neighboring genes and regulatory elements, but their contribution to disease pathogenesis is poorly understood. Here we show that TRIB1 is among the most robustly upregulated coding genes within the 8q24 amplicon in prostate cancer. Moreover, we demonstrate that TRIB1 amplification and overexpression are frequent in this tumor type. Importantly, we find that, parallel to its amplification, TRIB1 transcription is controlled by cMYC. Mouse modeling and functional analysis revealed that aberrant TRIB1 expression is causal to prostate cancer pathogenesis. In sum, we provide unprecedented evidence for the regulation and function of TRIB1 in prostate cancer.

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Section: Discussionsupporting

confidence: 89%

Genomic and Functional Regulation of TRIB1 Contributes to Prostate Cancer Pathogenesis

Shahrouzi

Astobiza

Cortazar

et al. 2020

Cancers

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“…5-Aza (an HMA) has been used as a standard of care in patients with higher-risk myelodysplastic syndromes, and in those with acute myeloid leukemia ineligible for intensive therapy [36]. Meanwhile, abnormal hypermethylation has been found to impact the expression of individual genes, and was associated with the malignant progression of solid cancer [37][38][39]. However, the use of HMAs in patients with cancer has never achieved a satisfactory and beneficial overall outcome, particularly with regard to the genetic and epigenetic complexity, as well as heterogeneity [40,41].…”

Section: Discussionmentioning

confidence: 99%

The Differential Antitumor Activity of 5-Aza-2'-deoxycytidine in Prostate Cancer DU145, 22RV1, and LNCaP Cells

Cheng¹,

Tang²,

Lian³

et al. 2021

J. Cancer

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DNA methylation is a DNA methyltransferase-mediated epigenetic modification affecting gene expression. This process is involved in the initiation and development of malignant disease. 5‐Aza‐2′‐deoxycytidine (5‐Aza), a classic DNA methyltransferase inhibitor, possesses antitumor proliferation activity. However, whether 5-Aza induces cytotoxicity in solid tumors warrants further investigated. In this study, human prostate cancer (CaP) cells were treated with 5-Aza and subjected to cell viability and cytotoxicity analysis. Reverse transcription-polymerase chain reaction and methylation-specific polymerase chain reaction assay were utilized to test the gene expression and methylation status of the p53 and p21 gene promoters. The results showed that 5-Aza differentially inhibited spontaneous proliferation, arrested the cell cycle at S phase in DU145, at G1 phase in 22RV1 and LNCaP cells, and G2 phase in normal RWPE-1 cells, as well as induced the expression of phospho-H2A.X and tumor suppressive mammary serine protease inhibitor (maspin) in all three types of CaP cells. 5-Aza also increased p53 and p21 transcription through promoter demethylation, and decreased the expression of oncogene c-Myc in 22RV1 and LNCaP cells. Western blotting analysis showed that the poly (ADP-ribose) polymerase cleavage was detected in DU145 and 22RV1 cells. Moreover, there were no significant changes in p53, p21 and c-Myc expression in DU145 cells following treatment with 5-Aza. Thus, in responsible for its apoptotic induction and DNA damage, the mechanism of the antitumor activities of 5-Aza may involve in an increase of tumor suppressive maspin, upregulation of wild type p53-mediated p21 expression and a decrease of oncogene c-Myc level in 22RV1 and LNCaP cells, and enhancing the tumor suppressive maspin expression in DU145 cells. These results enriched our understanding of the multifaceted antitumor activity of 5-Aza, and provided the expression basis of biomarkers for its possible clinical application in prostate cancer.

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“…A post hoc analysis of data from a Phase 3 trial showed that the detection of serum free methylated GSTP1 (mGSTP1) DNA can predict the outcome of chemotherapy in metastatic prostate cancer and may guide treatment decisions in the clinic [26]. In addition, methylation of other genes, including olfactory 4 (OLFM4) [27], MTSS1 [7] and myeloid ecotropic viral insertion site 2 prognosis has yet to be examined in a large prostate cancer dataset. In this study, we tried to explore a classi cation method that integrates several DNA methylation markers to help clinicians evaluate the therapeutic effect and prognosis of prostate cancer patients and choose treatment strategies.…”

Section: Discussionmentioning

confidence: 99%

“…These genes encompass many cellular functions, including cell cycle control, apoptosis, hormone response, DNA repair and damage prevention, signal transduction, tumor invasion and tumor suppression [5]. Frequent promoter methylation of genes such as glutathione S-transferase π (GSTP1) [6] metastasis suppressor 1 (MTSS1) [7] dedicator of cytokinesis 2 (DOCK2) [8] adenomatous polyposis coli (APC) [9] and retinoic acid receptor beta2(RARβ2) [10] has been found and is associated with the progression of prostate cancer. However, whether the methylation of these genes is related to important clinical factors, such as the degree of tumor malignancy and biochemical recurrence and prognosis, has not been determined from large datasets of patients with prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Prognosis in Patients with Prostate Cancer by DNA Methylation Classification

Chen

Pan

et al. 2020

Preprint

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Abstract Background: Prostate cancer is the second most frequently diagnosed cancer and the fifth leading cause of cancer-related death. It is estimated that the incidence of prostate cancer is on the rise worldwide. Epigenetic changes in tumors play an important role in the occurrence and development of prostate cancer. DNA methylation is one of the mechanisms of tumor epigenetic regulation and may be a new biomarker that has great potential in early tumor screening, treatment guidance and prognosis prediction. The purpose of this study was to explore a classification method from the perspective of DNA methylation.Methods: The least absolute shrinkage and selection operator (LASSO) method was used to analyze DNA methylation and RNA-seq data from the Cancer Genome Atlas (TCGA). The methylation sites with small differences were eliminated, and the 21 methylation sites with the most significant differences were retained for analysis. Using their corresponding gene expression levels, a recurrence prediction model for prostate cancer patients was constructed to distinguish high-risk, medium-risk, and low-risk cases. Immune cell abundance analysis, gene enrichment analysis, Tumor burden mutation analysis and gene copy number variation analysis were then used to analyze the differences among these three subtypes and their underlying mechanisms. Results: We observed the difference in disease-free survival (DFS) of the three methylated subtypes in the test set, which was verified in the validation set. We found three subtypes have different proportions of immune cells, especially in memory B cells, M2 macrophages, Treg cells. GSVA and GSEA analysis revealed that the relevant metastasis gene sets of prostate cancer were enriched in high-risk cases. In addition, the mutation frequencies of TP53, TTN and KMT2D were the highest, and gradually increased in the three genotypes according to Tumor burden mutation (TMB) analysis. Gene copy number variation (CNV) showed that AR, LAPTM4B, and MTDH were significantly amplified, while ATP1B2 and FAM92B were significantly deleted. Finally, univariate and multivariate analysis showed that there were statistical differences among the three methylation subtypes, which can be used as an index to predict prostate cancer recurrence.Conclusions: Our study suggests that classification based on DNA methylation is an independent factor for predicting tumor recurrence in patients with prostate cancer.

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MTSS1 hypermethylation is associated with prostate cancer progression

Cited by 11 publications

References 39 publications

Genomic and Functional Regulation of TRIB1 Contributes to Prostate Cancer Pathogenesis

Genomic and Functional Regulation of TRIB1 Contributes to Prostate Cancer Pathogenesis

The Differential Antitumor Activity of 5-Aza-2'-deoxycytidine in Prostate Cancer DU145, 22RV1, and LNCaP Cells

Prediction of Prognosis in Patients with Prostate Cancer by DNA Methylation Classification

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