ESCO2 inhibits tumor metastasis via transcriptionally repressing MMP2 in colorectal cancer

Guo, Xiongbo; Huang, Bin; Pan, Yinghua; Su, Shu-Guang; Li, Yan

doi:10.2147/cmar.s181265

Cited by 25 publications

(25 citation statements)

References 32 publications

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“…Fumiichiro and Miyako examined the genes change, found that up‐regulation of ESCO2 was striking in breast cancer tissues and cell lines . Notably, the dysregulated ESCO2 was implicated to adjust metastatic activity in colorectal cancer (CRC), suppressing Matrix Metallopeptidase 2 (MMP2) . Yet, whether and how the progression of RCC is controlled by ESCO2 has not been resolved.…”

Section: Introductionmentioning

confidence: 99%

Establishment of cohesion 1 homolog 2 facilitates cell aggressive behaviors and induces poor prognosis in renal cell carcinoma

Wang

Liu

2020

Clinical Laboratory Analysis

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Background and aims Establishment of cohesion 1 homolog 2 (ESCO2) has been identified as an essential factor for cohesion in cell cycle in human multiple cancers. Nonetheless, its functional implication on prognosis and cellular behaviors of renal cell carcinoma (RCC) is rarely elucidated. We performed this study to detect the effects of ESCO2 in RCC progression. Methods We accessed The Cancer Genome Atlas (TCGA) database to evaluate the ESCO2 expression levels in tumor tissues, including 32 normal tissues and 289 tumor tissues. Quantitative real‐time PCR and Western blot were implemented for expression detection. After ESCO2 knockdown using siRNAs interference, functional experiments were conducted to explore the role of ESCO2, such as cell proliferation analysis and colony formation assay. Transwell assays for migration and invasion was also performed. Results In this study, ESCO2 was significantly increased in RCC tissues and cell lines. The RCC patients with high expression of ESCO2 were susceptible to unfavorable prognosis, and its expression has a marked association with clinical features containing age, gender, pathologic stage, and so on. Furthermore, knockdown of ESCO2 inhibited cell growth, invasion, and migration. Mechanistically, phosphorylation protein kinase B (AKT) and mammalian target of rapamycin (mTOR), proliferating cell nuclear antigen (PCNA), and p53 were all down‐regulated due to the ESCO2 inhibition. Conclusions Therefore, our results raised the possibility that ESCO2 may act as a promising option for tumor therapeutic interference by exhibiting enhanced selectivity over conventional chemotherapy.

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Section: Introductionmentioning

confidence: 99%

Establishment of cohesion 1 homolog 2 facilitates cell aggressive behaviors and induces poor prognosis in renal cell carcinoma

Wang

Liu

2020

Clinical Laboratory Analysis

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“…SLC16A10, coding for a member of a family of plasma membrane amino acid transporters, was shown to be significantly upregulated in higher-grade gliomas [52]; however, its role in glioma and other cancer types remains unclear. ESCO2, required for the establishment of sister chromatid cohesion during the S phase of mitosis [53], can enhance the malignancy of gastric cancer while inhibiting colorectal tumor metastasis [54,55], and its role in glioma has not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics Prognostic Analysis of Lysine Acetylation Regulators in Glioma

et al. 2020

Preprint

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Background: Lysine acetylation is a crucial kind of protein modification and is related to the malignant development of various cancers. But their roles in glioma are still unclear and needed concluded comprehensively. Methods: In this study, we comprehensively analyzed the expression levels of 33 lysine acetylation regulators (LARs) and prognostic roles by using public data, including the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). The prognostic roles of LARs were judged by univariate Cox regression. Consensus clustering was applied to result in three stratified glioma subtypes (LA1, 2, and 3) with different clinical outcomes. We also constructed a risk signature for predicting the overall survival of glioma patients by using least absolute shrinkage and selection operator regression (LASSO regression). Besides, copy number variations (CNVs) and single nucleotide polymorphism (SNP) of LARs were also analyzed in our study. Results: We found the mRNA expression levels of most of LARs were dysregulated in gliomas and associated with the prognosis of glioma patients. The risk signature constructed by 14 LARs presented an independent prognostic role in both the CGGA (HR:1.96, 95%CI:1.33-2.90) and TCGA (HR:1.48, 95%CI:1.08-2.03) datasets and robust predictive effects in the ROC curves with all of area under curves more than 0.800. Moreover, the copy number variations of LARs were also significantly related to the prognosis of glioma patients, in which HDAC1 (1p) was one of the oncogenes lost in 1p/19q codeletion events, while SIRT2 (19q) and EP300 (22q) may act as tumor suppressors in gliomas with 19q or 22q deletions, respectively. Conclusion: LARs are potential biomarkers for the malignant progression of gliomas, and our results could be useful for predicting the OS of glioma patients and provide some clues in searching the functions of LARs in glioma progression. Keywords: glioma, lysine acetylation regulator, epigenetic, prognostic signature, biomarker.

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“…Genistein modulated the expression of histone acetyltransferases (Figure 2). The function of ESCO2 is to block MMP2 and help apoptosis [37]. Genistein upregulates the expression of ESCO2, which is likely to impact its anti-migratory response.…”

Section: Discussionmentioning

confidence: 99%

Genistein Modulates Signaling Pathways and Targets Several Epigenetic Markers in HeLa Cells

Sundaram

Unni

Somvanshi

et al. 2019

Genes

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Background: Several epigenetic changes are responsible for transcriptional alterations of signaling pathways and tumour suppressor genes (TSGs) contributing to carcinogenesis. This study was aimed to examine the effect of the phytochemical, genistein on various molecular targets in HeLa cells. Methods: Quantitative PCR was used to analyze the expression of various molecular targets. Biochemical assays were employed to study the epigenetic enzymes. To correlate the transcriptional status of the selected TSGs and epigenetic modulation, their promoter 5'CpG methylation levels were evaluated by quantitative methylation array followed by methylation specific restriction digestion. Results: The expression of several genes involved in the cell cycle regulation, migration, inflammation, phosphatidylinositol 3-kinase (PI3K) and mitogen activated kinase-like protein (MAPK) pathway were found to be modulated including CCNB1, TWIST1, MMP14, TERT, AKT1, PTPRR, FOS and IL1A. Genistein modulated the expression of DNA methyltransferases (DNMTs), histone deacetylases (HDACs), histone methyltransferases (HMTs), demethylases, and histone phosphorylases. Furthermore, genistein decreased the activity of DNMTs, HDACs, and HMTs and reduced global DNA methylation levels. Promoter methylation of several TSGs, including FHIT, RUNX3, CDH1, PTEN, and SOC51, was lowered with corresponding transcriptional increase. Network analysis indicated similar effect of genistein. Conclusion: This study presents a comprehensive mechanism of action of genistein showcasing effective epigenetic modulation and widespread transcriptional changes resulting in restoration of tumour suppressor gene expression. This study corroborates the development of genistein as a candidate for anti-cancer therapy.

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ESCO2 inhibits tumor metastasis via transcriptionally repressing MMP2 in colorectal cancer

Cited by 25 publications

References 32 publications

Establishment of cohesion 1 homolog 2 facilitates cell aggressive behaviors and induces poor prognosis in renal cell carcinoma

Establishment of cohesion 1 homolog 2 facilitates cell aggressive behaviors and induces poor prognosis in renal cell carcinoma

Multi-omics Prognostic Analysis of Lysine Acetylation Regulators in Glioma

Genistein Modulates Signaling Pathways and Targets Several Epigenetic Markers in HeLa Cells

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