EZH2 upregulation correlates with tumor invasiveness, proliferation, and angiogenesis in human pituitary adenomas

Liu, Bin; Pang, Bo; Wang, Qirui; Yang, Shengji; Gao, Taihong; Ding, Qian; Liu, Huajie; Yang, Yihang; Fan, Haitao; Zhang, Rui; Xin, Tao; Xu, Guofeng; Pang, Qi

doi:10.1016/j.humpath.2017.03.028

Cited by 15 publications

(13 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EZH2 and SUZ12, as two core components of PRC2 complex, have been shown to be involved in cancer progression [37-39]. In this study, we examined EZH2 expression in 50 CRC tissue samples and adjacent non-tumor tissue samples.…”

Section: Resultsmentioning

confidence: 99%

Long Non-Coding RNA SH3PXD2A-AS1 Promotes Cell Progression Partly Through Epigenetic Silencing P57 and KLF2 in Colorectal Cancer

Peng

Zhou

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies worldwide. Current evidence has revealed the key roles of long non-coding RNAs (IncRNAs) in multiple cancers, including CRC. In this study we identified the lncRNA SH3PXD2A-AS1 as a novel molecule associated with CRC progression by analyzing the publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to examine the expression levels of SH3PXD2A-AS1 in CRC tissue samples and CRC cell lines. Cell viability examination, colony-formation experiments, ethynyl deoxyuridine (Edu) assays and flow cytometry were performed to investigate the roles of SH3PXD2A-AS1 in CRC proliferation, cell cycle regulation, and apoptosis. Transwell assays were used to explore the effects of SH3PXD2A-AS1 on CRC cells migration and invasion. A nude mice model was used to assess the effects of SH3PXD2A-AS1 on tumorigenesis in vivo. Subcellular fractionation, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assays were conducted to detect the molecular mechanisms of SH3PXD2A-ASl-mediated gene expression. Rescue assays were used to determine whether P57 and Kruppel-like factor 2 (KLF2) were involved in SH3PXD2A-ASl-dependent CRC proliferation. Results: We firstly found that SH3PXD2A-AS1 was significantly upregulated in CRC tissues and cell lines, and overexpression of SH3PXD2A-AS1 was correlated with tumor size, TNM stage, and lymph node metastasis in patients with CRC. Furthermore, SH3PXD2A-AS1 knockdown inhibited CRC cells proliferation, migration and invasion in vitro, and suppressed tumorigenesis in vivo. Mechanistic studies indicated that SH3PXD2A-AS1 could epiqenetically repress P57 and KLF2 expression through interaction with EZH2. Rescue experiments suggested that SH3PXD2A-ASl-mediated oncogenesis was impaired by overexpression of P57 or KLF2. Interestingly, the expression of SH3PXD2A-AS1 was inversely correlated with the expression of P57 and KLF2 in CRC tissue samples. Conclusion: Our research presents the first evidence that SH3PXD2A-AS1 acts as an oncogene in CRC, and may be a promising diagnostic or therapeutic target in patients with CRC.

show abstract

Section: Resultsmentioning

confidence: 99%

Long Non-Coding RNA SH3PXD2A-AS1 Promotes Cell Progression Partly Through Epigenetic Silencing P57 and KLF2 in Colorectal Cancer

Peng

Zhou

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Indeed, increased expression of the extracellular matrix glycoprotein Tenascin-C (TNC) correlates with the H3K27M mutation in DIPG and experimental manipulation of TNC expression levels reveals a direct role of TNC in DIPG cell invasive behavior, at least in vitro (31). In addition, EZH2 has been shown to be required for the proper migration of neurons into the pons during development (32) and upregulation of EZH2 has been implicated in invasion in a variety of cancers (33)(34)(35)(36). Therefore, FIGURE 1 | Tumor cell-intrinsic alterations that can contribute to DIPG invasion and strategies for their therapeutic targeting.…”

Section: H3k27mmentioning

confidence: 99%

Invaders Exposed: Understanding and Targeting Tumor Cell Invasion in Diffuse Intrinsic Pontine Glioma

et al. 2020

View full text Add to dashboard Cite

Diffuse Intrinsic Pontine Glioma (DIPG) is a rare, highly aggressive pediatric brain tumor that originates in the pons. DIPG is untreatable and universally fatal, with a median life expectancy of less than a year. Resection is not an option, due to the anatomical location of the tumor, radiotherapy has limited effect and no chemotherapeutic or targeted treatment approach has proven to be successful. This poor prognosis is partly attributed to the tumor's highly infiltrative diffuse and invasive spread. Thus, targeting the invasive behavior of DIPG has the potential to be of therapeutic value. In order to target DIPG invasion successfully, detailed mechanistic knowledge on the underlying drivers is required. Here, we review both DIPG tumor cell's intrinsic molecular processes and extrinsic environmental factors contributing to DIPG invasion. Importantly, DIPG represents a heterogenous disease and through advances in whole-genome sequencing, different subtypes of disease based on underlying driver mutations are now being recognized. Recent evidence also demonstrates intra-tumor heterogeneity in terms of invasiveness and implies that highly infiltrative tumor subclones can enhance the migratory behavior of neighboring cells. This might partially be mediated by "tumor microtubes," long membranous extensions through which tumor cells connect and communicate, as well as through the secretion of extracellular vesicles. Some of the described processes involved in invasion are already being targeted in clinical trials. However, more research into the mechanisms of DIPG invasion is urgently needed and might result in the development of an effective therapy for children suffering from this devastating disease. We discuss the implications of newly discovered invasive mechanisms for therapeutic targeting and the challenges therapy development face in light of disease in the developing brain.

show abstract

“…However, to date no single marker has been found to be unequivocally related to tumor behavior. Liu et al [150] recently described that EZH2 protein and mRNA expression are upregulated in invasive compared with non-invasive PitNETs, and that expression of EZH2 also correlated with the proliferation index. Interestingly, the same author also suggested that matrix metalloproteinase MMP-14 is significantly overexpressed in invasive PitNETs and correlates with EZH2 expression, indicating that both molecules are useful markers of invasiveness.…”

Section: Pathological and Molecular Considerationsmentioning

confidence: 99%

Pituitary Adenomas and Invasiveness from Anatomo-Surgical, Radiological, and Histological Perspectives: A Systematic Literature Review

Serioli

Doglietto

Fiorindi

et al. 2019

Cancers

View full text Add to dashboard Cite

Invasiveness in pituitary adenomas has been defined and investigated from multiple perspectives, with varying results when its predictive value is considered. A systematic literature review, following PRISMA guidelines, was performed, searching PubMed and Scopus databases with terms that included molecular markers, histological, radiological, anatomical and surgical data on invasiveness of pituitary adenomas. The results showed that differing views are still present for anatomical aspects of the sellar region that are relevant to the concept of invasiveness; radiological and histological diagnoses are still limited, but might improve in the future, especially if they are related to surgical findings, which have become more accurate thanks to the introduction of the endoscope. The aim is to achieve a correct distinction between truly invasive pituitary adenomas from those that, in contrast, present with extension in the parasellar area through natural pathways. At present, diagnosis of invasiveness should be based on a comprehensive analysis of radiological, intra-operative and histological findings.

show abstract

EZH2 upregulation correlates with tumor invasiveness, proliferation, and angiogenesis in human pituitary adenomas

Cited by 15 publications

References 41 publications

Long Non-Coding RNA SH3PXD2A-AS1 Promotes Cell Progression Partly Through Epigenetic Silencing P57 and KLF2 in Colorectal Cancer

Long Non-Coding RNA SH3PXD2A-AS1 Promotes Cell Progression Partly Through Epigenetic Silencing P57 and KLF2 in Colorectal Cancer

Invaders Exposed: Understanding and Targeting Tumor Cell Invasion in Diffuse Intrinsic Pontine Glioma

Pituitary Adenomas and Invasiveness from Anatomo-Surgical, Radiological, and Histological Perspectives: A Systematic Literature Review

Contact Info

Product

Resources

About