SUZ12 promotes gastric cancer cell proliferation and metastasis by regulating KLF2 and E-cadherin

Xia, Rui; Jin, Feiyan; Lǚ, Kai; Wan, Li; Xie, Min; Xu, Tongpeng; De, Wei; Wang, Zhao-xia

doi:10.1007/s13277-015-3195-7

Cited by 44 publications

(47 citation statements)

References 31 publications

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“…There is evidence showed that its expression is diminished in multiple cancers and possesses tumor-suppressor features for its inhibitory effects on cell proliferation [31, 32], and our previous study showed that SUZ12 could repress its expression in gastric cancer cells [33]. In this study, we also found that KLF2 can function as tumor suppressor and its' expression could be suppressed by ZFAS1 through recruiting EZH2 and LSD1 to its promoter region in gastric cancer cells.…”

Section: Discussionsupporting

confidence: 61%

Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression

et al. 2016

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Recently, long noncoding RNAs have been emerged as critical regulators of human disease and prognostic markers in several cancers, including gastric cancer. In this study, we globally assessed the transcriptomic differences of lncRNAs in gastric cancer using publicly available microarray data from Gene Expression Omnibus (GEO) and identified an oncogenetic lncRNA ZFAS1, which may promote gastric tumorigenesis. ZFAS1 has been found to be upregulated and function as oncogene in colorectal cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in gastric cancer is still undetermined. Here, we reported that ZFAS1 expression is also overexpressed in gastric cancer, and its increased level is associated with poor prognosis and shorter survival. Knockdown of ZFAS1 impaired gastric cancer cells proliferation and induced apoptosis in vitro, and inhibited tumorigenicity of gastric cancer cells in vivo. Mechanistically, RNA immunoprecipitation and RNA pull-down experiment showed that ZFAS1 could simultaneously interact with EZH2 and LSD1/CoREST to repress underlying targets KLF2 and NKD2 transcription. In addition, rescue experiments determined that ZFAS1 oncogenic function is partly dependent on repressing KLF2 and NKD2. Taken together, our findings illuminate how ZFAS1 over-expression confers an oncogenic function in gastric cancer.

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Section: Discussionsupporting

confidence: 61%

Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression

et al. 2016

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“…Inhibition of PI M2 is a promising avenue for the treatment of multiple myeloma 65 . Su(z)12 is part of the ubiquitous polycomb repressive complex 2 (PRC2) and is overexpressed in numerous cancers, including gastric cancer where Su(z)12 levels were associated with increased metastasis and unfavorable survival prognosis 67 . The ETS family of transcription factors has demonstrated significant involvement in all stages of tumorigenesis 68 , while FoxA1 is known as ‘pioneer transcription factor in organogenesis and cancer progression’ 69 .…”

Section: Resultsmentioning

confidence: 99%

Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells

Mihaylova

Abnave

Kao

et al. 2017

Preprint

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Background 21The family of Mixed Lineage Leukaemia (MLL) histone methyltransferase 22 proteins is often implicated in disease processes, particularly cancer. We 23 focus on the tumour suppressors MLL3 and MLL4, which are mutated in a 24 high percentage of cancers, but very little is known about the underlying 25 transcriptional and epigenetic changes that contribute to malignancy. 26 Results 27Here we make use of the highly accessible planarian model system to 28 uncover a role for MLL3/4 orthologs in controlling stem cell differentiation 29 and proliferation, suggesting conservation of tumour suppressor function 30 over a large evolutionary timescale for these epigenetic regulators. 31Knockdown of the planarian Mll3/4 orthologs compromises stem cell 32 differentiation and leads to hyper-proliferation and tumour-like outgrowth 33formation. The planarian system allows us to investigate the early-stage 34 epigenetic and transcriptional changes in cells that will go on to form 35 tumours after loss of MLL3/4 function, identifying genome wide alterations 36 that occur early in the development of the pathology. This reveals mis-37 regulation of both conserved and hypothesised oncogenes and tumour 38 suppressors, that together likely explain the cancer-like phenotype 39 observed in planarians. 40 Conclusions 41We confirm MLL3/4 tumour suppressor function and uncover a deep 42 conservation of this role in stem cells. We find potentially conserved mis-43 regulated downstream targets driving the effects of MLL3/4 loss of function. 44Our work demonstrates the suitability of planarians for the study of 45 epigenetic phenotypes related to cancer and stem cell function, and for 46 capturing early causative changes in a definitive population of tumour 47 forming stem cells in vivo. 48 49 50 51. CC-BY-NC 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/126540 doi: bioRxiv preprint first posted online Apr. 11, 2017; 52 53 Background 54The pluripotent adult stem cell (pASC) population of planarian flatworms is a 55 highly accessible study system to elucidate fundamental aspects of stem cell 56 function 1,2 . These stem cells, collectively known as neoblasts (NBs), bestow 57 these animals with an endless capacity to regenerate all the organs and 58 tissues of this relatively simple organism after amputation. Comparisons of 59 stem cell expression profiles and available functional data between planarians 60 and other simpler animals with mammals show that key aspects of stem cell 61 biology are deeply conserved [3][4][5][6][7][8][9] . Thus, studies of the NB population have the 62 potential to inform us about the origins of fundamental stem cell properties 63 and behaviors such as maintenance of genome stability 10 , self-renewal 7,11 , 64 pluripotency 12-15 , differentiation [16][17][18] and migration 19,20 . All of these are highl...

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“…SNAI1-PRC2 interaction can also be bridged by Ajuba LIM, PRMT5 or a mediator protein MEP50 [135,136]. In gastric cancer cells, PRC2 is also recruited through SUZ12 and catalyzes H3K27me3 on KLF2 and E-cadherin promoters [137]. Intriguingly, an H3K4me3 to H3K27me3 switch was observed on 102 EMT marker gene promoters including E-cadherin in a TWIST1-induced EMT cell model.…”

Section: Permissive Histone Modifications In Emtmentioning

confidence: 99%

Epigenetic regulation of epithelial–mesenchymal transition

Sun

Fang

2016

Cell. Mol. Life Sci.

109

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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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SUZ12 promotes gastric cancer cell proliferation and metastasis by regulating KLF2 and E-cadherin

Cited by 44 publications

References 31 publications

Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression

Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression

Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells

Epigenetic regulation of epithelial–mesenchymal transition

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