Snail and Slug collaborate on EMT and tumor metastasis through miR-101-mediated EZH2 axis in oral tongue squamous cell carcinoma

Zheng, Min; Jiang, Yaping; Chen, Wei; Li, Kaide; Liu, Xin; Gao, Siyang; Feng, Hao; Wang, Shasha; Jiang, Jian; Ma, Xiangrui; Cen, Xiao; Tang, Ya‐Jie; Chen, Yu; Lin, Yunfeng; Tang, Yaling; Liang, Xin‐hua

doi:10.18632/oncotarget.3180

Cited by 104 publications

(81 citation statements)

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“…They also target mRNA of several chromatin modifying enzymes, such as BMI1, SUZ12 and SIRT1 to negatively regulate EMT and CSC-like properties [230–232]. In tongue cancer cells, SNAI1/2 recruits PRC2 to suppress transcription of miR-101 which also targets 3’-UTR of EZH2 mRNA [233], representing another axis of miRNA signaling for EMT [234]. Furthermore, mRNA of SNAI1/2 and TWIST1/2 is targeted by different large groups of miRNAs while the reciprocal regulatory loop was not reported [220].…”

Section: Microrna and Lncrnas In Emtmentioning

confidence: 99%

Epigenetic regulation of epithelial–mesenchymal transition

Sun

Fang

2016

Cell. Mol. Life Sci.

111

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Epithelial-mesenchymal transition (EMT) is an essential process for morphogenesis and organ development which reversibly enables polarized epithelial cells to lose their epithelial characteristics and acquire mesenchymal properties. It is now evident that the aberrant activation of EMT is also a critical mechanism to endow epithelial cancer cells with migratory and invasive capabilities associated with metastatic competence. This dedifferentiation program is mediated by a small cohort of pleiotropic transcription factors which in turn orchestrate a complex array of epigenetic mechanisms for the widespread changes in gene expression. Here, we review major epigenetic mechanisms with emphasis on histone modifications and discuss their implications in EMT and tumor progression. We also highlight mechanisms underlying transcription regulation concerted by various chromatin modifying proteins and EMT-inducing transcription factors at different molecular layers. Owing to the reversible nature of epigenetic modifications, a thorough understanding of their functions in EMT will not only provide new insights into our knowledge of cancer progression and metastasis, but also facilitates the development of diagnostic and therapeutic strategies for human malignancy.

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Section: Microrna and Lncrnas In Emtmentioning

confidence: 99%

Epigenetic regulation of epithelial–mesenchymal transition

Sun

Fang

2016

Cell. Mol. Life Sci.

111

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“…Mechanistically, EZH2 can directly induce EMT by repressing the expression of E-cadherin through histone H3K27 trimethylation 29 , or indirectly initiate EMT by inhibiting the expression of miR-361 (a suppressor of known EMT inducer Twist) 30 . In addition, several miRNAs have been reported to suppress EMT through EZH2 31, 32 .…”

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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“…Despite tremendous improvements in treatment by surgery, radiotherapy, and chemotherapy over the past decades, the prognosisforpatientswithHNOSCCshasnotchanged. HNOSCC is a disease that can arise in various anatomic locations, including the oral cavity, tongue, pharynx,andlarynx.Oraltonguesquamouscellcarcinoma(OTSCC)isoneofthemostcommontypesof HNOSCCandissignificantlymoreaggressivethan other forms of HNOSCC in terms of local invasion andspread.Althoughsomeofthemolecularevents underlyingthiscomplexdiseasehavebeenidentified, thepathwaysinvolvedinthedevelopmentandprogression of squamous cell carcinoma of the tongue arestillpoorlyunderstood [2,3,4,5].…”

Section: Introductionmentioning

confidence: 99%