microRNA miR-200b affects proliferation, invasiveness and stemness of endometriotic cells by targeting ZEB1, ZEB2 and KLF4

Eggers, Julia C.; Martino, Valentina; Reinbold, Rolland; Schäfer, Sebastian D.; Kiesel, L.; Starzinski‐Powitz, Anna; Schüring, Andreas N.; Kemper, Björn; Greve, Burkhard; Götte, Martin

doi:10.1016/j.rbmo.2015.12.013

Cited by 74 publications

(59 citation statements)

References 75 publications

(107 reference statements)

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“…MicroRNA miR-200b affects cell proliferation, cell invasion and stemness of endometriotic cells by targeting ZEB1, ZEB2 and KLF4 [24]. miR-200b inhibits migration and invasion in NSCLC cells via targeting FSCN1 [25].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of lncRNA HOXA11-AS promotes cell epithelial–mesenchymal transition by repressing miR-200b in non-small cell lung cancer

Chen

Zhou

et al. 2017

Cancer Cell Int

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BackgroundRecent studies have verified that long noncoding RNAs (lncRNAs) involved in many biological functions and play crucial roles in human cancers progression, the study aimed to detect the association between long non-coding RNA HOXA11-AS and epithelial–mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC).MethodsThe lncRNA HOXA11-AS expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assays in 78 paired of tumor tissue and adjacent normal tissue samples in NSCLC patients. Kaplan–Meier survival curves and log-rank test was used to examine the association between lncRNA HOXA11-AS expression and the over survival time in NSCLC patients. Transwell invasion assay was performed to detect the cell invasion ability. QRT-PCR and western-blot analysis detected the mRNA and protein expression of EMT related transcription factors ZEB1/ZEB2, Snail1/2 and EMT marker E-cadherin and N-cadherin in NSCLC cells. RIP and Chromatin immunoprecipitation assays were performed to analyze the association between lncRNA HOXA11-AS and miR-200b expression in NSCLC cells.ResultsThe lncRNA HOXA11-AS expression levels were significantly higher in NSCLC tissues compared with adjacent normal tissues and higher HOXA11-AS expression levels had a poor prognosis in NSCLC patients. Furthermore, knockdown of lncRNA HOXA11-AS in A549 and H1299 cells dramatically inhibited cell invasive abilities. Besides, the transcription levels and protein levels of EMT related transcription factors ZEB1/ZEB2, Snail1/2, and EMT maker N-cadherin were down-regulated after lncRNA HOXA11-AS was knocked down, but the mRNA and protein expression levels of EMT maker E-cadherin was increasing in A549 and H1299 cells. The mechanistic findings showed demonstrated that HOXA11-AS interacted with EZH2 and DNMT1 and recruited them to the miR-200b promoter regions to repress miR-200b expression in NSCLC cells, which promoted cell EMT in NSCLC.ConclusionsOur results showed that up-regulation of lncRNA HOXA11-AS predicted a poor prognosis and lncRNA HOXA11-AS promoted cell epithelial–mesenchymal transition (EMT) by inhibiting miR-200b expression in NSCLC.

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Section: Discussionmentioning

confidence: 99%

Overexpression of lncRNA HOXA11-AS promotes cell epithelial–mesenchymal transition by repressing miR-200b in non-small cell lung cancer

Chen

Zhou

et al. 2017

Cancer Cell Int

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“…Indeed, to date several factors have been shown to regulate EMT in endometriosis and adenomyosis, including estrogen 11 , Wnt/β-catenin 2 , lipocalin 2 12 , hepatocyte growth factor (HGF) 2, 13, 14 , lysyl oxidase 15 , periostin 16 , hypoxia 17 , microRNA-200b (miR-200b) 18 , platelets 7 and possibly Myc 19 and LSD1 20 . It becomes clear that EMT not only increases cellular invasiveness but also promotes fibrogenesis 7, 21 .…”

Section: Introductionmentioning

confidence: 99%

Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis

Zhang

Dong

Liu

et al. 2017

Sci Rep

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EZH2, a subunit of the polycomb repressive complex 2 (PRC2) catalyzing trimethylation of histone H3 lysine 27 (H3K27), induces epithelial-mesenchymal transition (EMT) in cancers. However, whether EZH2 regulates EMT in endometriosis is unclear. Here, we show that EZH2 expression, along with its associated PRC2 proteins, is significantly elevated in ectopic and eutopic endometrium from women with endometriosis as compared with control endometrium. EZH2 knockdown or inhibition restored the epithelial phenotypes of endometriotic epithelial cells, concomitant with the upregulation of E-cadherin and downregulation of vimentin and transcription factors (Snail and Slug) as well as reduced cellular migratory and invasive propensity. Conversely, overexpression of EZH2 induced the expression of Snail, Slug and vimentin and suppresses E-cadherin expression. In vivo administration of 3-Deazaneplanocin A (DZNep), an EZH2 inhibitor, significantly inhibited the growth of endometriotic lesions and improved generalized hyperalgesia, along with attenuated EMT and reduced fibrosis in endometriosis. Notably, platelets induced EZH2 upregulation and increased H3K27 and H3K9 trimethylation levels in endometriotic epithelial cells. These data identify EZH2 as a novel driver of EMT in endometriosis, implicates the link between wound healing and epigenetic changes in the context of endometriosis, and underscore the role of platelets in the development of endometriosis.

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“…Zeb1 , a transcription factor containing 1117 amino acids, is an EMT marker in cancer metastasis of some tissues including kidney [10,11]. Zeb1 promotes EMT through suppression of CDH1 (encoding E-cadherin, an epithelial maker) and the microRNA-200 [10].…”

Section: Introductionmentioning

confidence: 99%

“…Zeb1 promotes EMT through suppression of CDH1 (encoding E-cadherin, an epithelial maker) and the microRNA-200 [10]. This process activates transforming growth factor-β1 (TGF-β1) signaling pathway and trigger cancer cell proliferation, invasiveness and stemness out of control [11,12]. In addition, Zeb1 also plays a critical role in animal organ development [13], cartilage development [14] and regulation of mesenchymal cell proliferation [15].…”

Section: Introductionmentioning

confidence: 99%

Zeb1 Is a Potential Regulator of Six2 in the Proliferation, Apoptosis and Migration of Metanephric Mesenchyme Cells

Zhao

Zhou

et al. 2016

IJMS

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Nephron progenitor cells surround around the ureteric bud tips (UB) and inductively interact with the UB to originate nephrons, the basic units of renal function. This process is determined by the internal balance between self-renewal and consumption of the nephron progenitor cells, which is depending on the complicated regulation networks. It has been reported that Zeb1 regulates the proliferation of mesenchymal cells in mouse embryos. However, the role of Zeb1 in nephrons generation is not clear, especially in metanephric mesenchyme (MM). Here, we detected cell proliferation, apoptosis and migration in MM cells by EdU assay, flow cytometry assay and wound healing assay, respectively. Meanwhile, Western and RT-PCR were used to measure the expression level of Zeb1 and Six2 in MM cells and developing kidney. Besides, the dual-luciferase assay was conducted to study the molecular relationship between Zeb1 and Six2. We found that knock-down of Zeb1 decreased cell proliferation, migration and promoted cell apoptosis in MM cells and Zeb1 overexpression leaded to the opposite data. Western-blot and RT-PCR results showed that knock-down of Zeb1 decreased the expression of Six2 in MM cells and Zeb1 overexpression contributed to the opposite results. Similarly, Zeb1 promoted Six2 promoter reporter activity in luciferase assays. However, double knock-down of Zeb1 and Six2 did not enhance the apoptosis of MM cells compared with control cells. Nevertheless, double silence of Zeb1 and Six2 repressed cell proliferation. In addition, we also found that Zeb1 and Six2 had an identical pattern in distinct developing phases of embryonic kidney. These results indicated that there may exist a complicated regulation network between Six2 and Zeb1. Together, we demonstrate Zeb1 promotes proliferation and apoptosis and inhibits the migration of MM cells, in association with Six2.

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microRNA miR-200b affects proliferation, invasiveness and stemness of endometriotic cells by targeting ZEB1, ZEB2 and KLF4

Cited by 74 publications

References 75 publications

Overexpression of lncRNA HOXA11-AS promotes cell epithelial–mesenchymal transition by repressing miR-200b in non-small cell lung cancer

Overexpression of lncRNA HOXA11-AS promotes cell epithelial–mesenchymal transition by repressing miR-200b in non-small cell lung cancer

Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis

Zeb1 Is a Potential Regulator of Six2 in the Proliferation, Apoptosis and Migration of Metanephric Mesenchyme Cells

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