EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer

Han, Ting; Jiao, Feng; Hu, Hai; Yuan, Cuncun; Wang, Lei; Jin, Ziliang; Shi, Weifeng

doi:10.18632/oncotarget.7156

Cited by 79 publications

(72 citation statements)

References 51 publications

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“…EZH2 was previously shown to repress E-cadherin in breast, pancreatic and prostate cancer cells [40, 41]. Cooperation between Snail1 and EZH2 in the repression of E-cadherin was also observed during neural crest development [42].…”

Section: Discussionmentioning

confidence: 99%

EZH2 inhibition promotes epithelial-to-mesenchymal transition in ovarian cancer cells

et al. 2016

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Cancer cells acquire essential characteristics for metastatic dissemination through the process of epithelial-to-mesenchymal transition (EMT), which is regulated by gene expression and chromatin remodeling changes. The enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2 (PRC2), catalyzes trimethylation of lysine 27 of histone H3 (H3K27me3) to repress gene transcription. Here we report the functional roles of EZH2-catalyzed H3K27me3 during EMT in ovarian cancer (OC) cells. TGF-β-induced EMT in SKOV3 OC cells was associated with decreased levels of EZH2 and H3K27me3 (P<0.05). These effects were delayed (~72 h relative to EMT initiation) and coincided with increased (>15-fold) expression of EMT-associated transcription factors ZEB2 and SNAI2. EZH2 knockdown (using siRNA) or enzymatic inhibition (by GSK126) induced EMT-like changes in OC cells. The EMT regulator ZEB2 was upregulated in cells treated with either approach. Furthermore, TGF-β enhanced expression of ZEB2 in EZH2 siRNA- or GSK126-treated cells (P<0.01), suggesting that H3K27me3 plays a role in TGF-β-stimulated ZEB2 induction. Chromatin immunoprecipitation assays confirmed that TGF-β treatment decreased binding of EZH2 and H3K27me3 to the ZEB2 promoter (P<0.05). In all, these results demonstrate that EZH2, by repressing ZEB2, is required for the maintenance of an epithelial phenotype in OC cells.

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Section: Discussionmentioning

confidence: 99%

EZH2 inhibition promotes epithelial-to-mesenchymal transition in ovarian cancer cells

et al. 2016

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“…Glutathione‐S‐transferase pull‐down and RIP assays demonstrated that the 3′‐end of MALAT1 interacts with the N‐terminal of EZH2. MALAT1 can mediate tumor progression and chemotherapy resistance by recruiting EZH2 to chromatin loci, such as E‐cadherin, protocadherin 10, p21, and p27 (Han, Jiao et al, ; Hirata et al, ; Qi et al, ; Wang, Ding et al, ; Wang, Zhu et al, ). Malat1 also recruits suppressor of variegation 3‐9 homolog 1 (Suv39h1) to MyoD‐binding loci, causing trimethylation of histone 3 lysine 9 (H3K9me3), which suppresses the transcriptional activity of MyoD, which in turn represses myoblast differentiation (Chen, Zhao et al, ).…”

Section: Mechanisms By Which Malat1 Regulates Biological Functionsmentioning

confidence: 99%

Functions and regulatory mechanisms of metastasis‐associated lung adenocarcinoma transcript 1

Chen

Huang

et al. 2018

Journal Cellular Physiology

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Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA whose transcript is around 8 kb in length. As an important stress response molecule, MALAT1 can be expressed differently under stress conditions, such as hypoxia, high glucose, hydrogen peroxide, ultraviolet irradiation, infection, and chemical stimulation. MALAT1 is involved in regulating multiple cell behaviors, such as proliferation, apoptosis, differentiation, migration, epithelial-mesenchymal transition, autophagy, and morphological maintenance. Extensive evidence show that MALAT1 plays critical roles in the physiopathological process of embryo implantation, angiogenesis, tissue inflammation, tumor progression, liver fibrosis, cardiovascular remodeling, and diabetes progression by regulating gene transcription, forming RNA-protein complexes with proteins as a structural component, regulating protein activity, assisting protein localization, mediating epigenetic changes, or by acting as a competing endogenous RNA. Furthermore, MALAT1 can affect the sensitivity of chemotherapy and radiotherapy; therefore, it could be used as a potential drug target for chemotherapy and radiotherapy sensitization. The levels of MALAT1 are reported to be overexpressed in most tumor tissues or sera, and the expression levels of MALAT1 often affect the tumor size, stage, lymph node metastasis, and distant invasion. Therefore, MALAT1 can be used as a biomarker for early diagnosis, severity assessment, or prognostic assessment. This review outlines the current understanding of the biological role and function of MALAT1. In the meantime, we have summarized the mechanisms involved in the reulation of MALAT1 expression and the mechanisms by which MALAT1 regulates the physiological and pathological processes.

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“…1 Its mortality nearly equals its incidence rate, and its overall 5-year survival rate (~8%) has not improved over the last decade. 3,4 Due to these factors and specific anatomical features, only 15-20% of patients are diagnosed with resectable PC, while majority are diagnosed with locally advanced or metastatic disease associated with poor prognosis. 3,4 Due to these factors and specific anatomical features, only 15-20% of patients are diagnosed with resectable PC, while majority are diagnosed with locally advanced or metastatic disease associated with poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Long non‐coding RNA lnc‐PCTST predicts prognosis through inhibiting progression of pancreatic cancer by downregulation of TACC‐3

Wang

Ding

et al. 2018

Intl Journal of Cancer

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Pancreatic cancer (PC), which is one of the most lethal of malignancies and a major health burden, is associated with a dismal prognosis despite current therapeutic advances. Numerous long noncoding RNAs (lncRNA) have shown to be essential for PC tumorigenesis and progression. Nevertheless, the exact expression pattern of lnc-PCTST and its clinical significance still remain unclear. This study investigates the expression pattern of lnc-PCTST and its associated mRNA in three paired PC tissues and adjacent non-tumor tissues by Microarray-coarray approach. Briefly, our data demonstrated that lnc-PCTST expression is down-regulated in PC tissues. Also, lnc-PCTST has shown to be negatively correlated with transforming acidic coiled-coil 3 (TACC-3) expression. This expression pattern was further confirmed following qRT-PCR validation of 34 out of 48 paired cancer tissues. Furthermore, lnc-PCTST overexpression in PC cell lines inhibited cell proliferation and invasion in vitro, and tumorigenesis in vivo (using nude mice as animal model), but did not altered cell migration. Moreover, lnc-PCTST overexpression increased E-cadherin and repressed vimentin expression in vitro. Additionally, TACC-3 knockdown simulated the inhibiting effect of lnc-PCTST overexpression on PC cell lines, and the impaired proliferation, invasion effect and E-cadherin, vimentin expression on lnc-PCTST over-expressed cell lines can be rescued by overexpressed TACC-3. Significantly, the expression of lnc-PCTST was closely associated with its genomic neighboring gene TACC-3 and inhibited its promoter activity. In conclusion, lnc-PCTST is a potential tumor suppressor in PC, which inhibits cell proliferation, invasion, tumorigenesis and EMT by modulating TACC-3.

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EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer

Cited by 79 publications

References 51 publications

EZH2 inhibition promotes epithelial-to-mesenchymal transition in ovarian cancer cells

EZH2 inhibition promotes epithelial-to-mesenchymal transition in ovarian cancer cells

Functions and regulatory mechanisms of metastasis‐associated lung adenocarcinoma transcript 1

Long non‐coding RNA lnc‐PCTST predicts prognosis through inhibiting progression of pancreatic cancer by downregulation of TACC‐3

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