Setdb1, a novel interactor of ΔNp63, is involved in breast tumorigenesis

Regina, Carla; Compagnone, Mirco; Peschiaroli, Angelo; Lena, Anna Maria; Annicchiarico-Petruzzelli, Margherita; Piro, María Cristina; Melino, Gerry; Candi, Eleonora

doi:10.18632/oncotarget.7089

Cited by 37 publications

(34 citation statements)

References 63 publications

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“…Downregulation of SETDB1 in the BT549 and MDA-MB-231 cells reduced cell proliferation, whereas SETDB1 upregulation in MCF7 and T47D cells enhanced proliferation. Recently, Regina et al (29) reported that SETDB1 is overexpressed in breast cancer cell lines and enhanced tumor cell growth, which is consistent with the findings of the current study. Additionally, depletion of SETDB1 suppressed cell migration and invasion in vitro and reduced lung metastasis in vivo.…”

Section: Discussionsupporting

confidence: 93%

SETDB1 induces epithelial‑mesenchymal transition in breast carcinoma by directly binding with Snail promoter

Yang

Hou

et al. 2018

Oncol Rep

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SET domain bifurcated 1 (SETDB1) is a histone H3 lysine 9 methyltransferase that is highly expressed in various tumor types, including breast cancer. However, how SETDB1 functions in breast cancer is unclear. In the present study, proliferation, migration and invasion assays were performed to explore the role of SETDB1 in breast cancer cells. SETDB1 downregulation in BT549 and MDA-MB-231 cells reduced cell proliferation, whereas upregulation in MCF7 and T47D cells enhanced proliferation. Depletion of SETDB1 suppressed cell migration and invasion in vitro and reduced lung metastasis in vivo. By contrast, SETDB1 overexpression enhanced cell migration and invasiveness. Notably, SETDB1 overexpression appeared to induce epithelial-mesenchymal transition (EMT) in MCF7 cells. Mechanistic investigations indicated that SETDB1 acts as an EMT inducer by binding directly to the promoter of the transcription factor Snail. Thus, SETDB1 is involved in breast cancer metastasis and may be a therapeutic target for treating patients with breast cancer.

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Section: Discussionsupporting

confidence: 93%

SETDB1 induces epithelial‑mesenchymal transition in breast carcinoma by directly binding with Snail promoter

Yang

Hou

et al. 2018

Oncol Rep

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“…In this study, we identified the expression of SETDB1 and H3K9me1 were significantly upregulated in CCA tissues cells, as compared to that in normal tissues or HIBEC cell. These results suggested that SETDB1 were indeed up-regulated in CRC as well as in other solid tumors [22,24]. On the other hand, survivin is an oncogene that regulates the apoptosis, proliferation, and invasion of many cancers [25][26][27].…”

Section: Discussionmentioning

confidence: 86%

“…SETDB1 protein belongs to the SET-domain (Su(var)3-9, E(z), Thrithorax) protein methyltransferase family [21], which is mainly involved in tri-methylation of H3K9 and usually cause gene silencing or transcription inhibition. In recent years, mounting evidence has linked the aberrant high expression of SETDB1 to the human carcinogenesis, including melanoma, lung cancer, breast cancer, ovarian cancer [22][23][24]. Further investigations are ongoing to explore the underlying mechanism of epigenetic modifications by SETDB1.…”

Section: Discussionmentioning

confidence: 99%

LncRNA FENDRR represses proliferation, migration and invasion through suppression of survivin in cholangiocarcinoma cells

Qin

Zhou

et al. 2019

Cell Cycle

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This study was to investigate the biological function and underlying mechanisms of FENDRR in cholangiocarcinoma (CCA) cell proliferation, migration and invasion. FENDRR and survivin expression in CCA tissues or cell lines were measured by qRT-PCR. In QBC939 and HuCCTl cells, cell proliferation was detected by CCK-8, cell migration and invasion were using transwell assay. RNA pull-down and RIP assay were performed to determine whether FENDRR can combine with SETDB1 in CCA cell. The effect of SETDB1 on survivin and H3K9me1 expression in CCA cells were determined by western blotting. ChIP analysis was performed to analyze the combination of SETDB1 with survivin promoter in CCA cell. The effect of SETDB1 knockdown on survivin and H3K9me1 expression in CCA cells after transfection with FENDRR were determined by western blotting. The results showed that lncRNA FENDRR was downregulated in CCA tissues and cells, and was negatively correlated with survivin expression. Further investigation demonstrated that FENDRR represses CCA cell proliferation, migration and invasion through regulating survivin expression. FENDRR associated with SETDB1 and H3K9 to epigenetically silence survivin and then regulated cell proliferation, migration and invasion. These findings indicate an important role for FENDRR-survivin axis in CCA cell proliferation, migration and invasion, and reveal a novel epigenetic mechanism for survivin silencing. Our data indicated that FENDRR silences survivin via SETDB1-mediated H3K9 methylation, thereby represses CCA cell proliferation, migration and invasion. ARTICLE HISTORY

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“…However, it has been proposed that SETDB1 indirectly up-regulates STAT3 expression and induces TWIST and C-MYC to potentiate this process [125]. Alternatively, SETDB1 stabilizes ΔNp63α through protein interaction while ΔNp63α might recruit SETDB1 to repress multiple EMT-related genes [126]. Additionally, amplification of SETDB1 was observed in melanoma, lung and liver cancers [127–129].…”

Section: Permissive Histone Modifications In Emtmentioning

confidence: 99%

Epigenetic regulation of epithelial–mesenchymal transition

Sun

Fang

2016

Cell. Mol. Life Sci.

108

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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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Setdb1, a novel interactor of ΔNp63, is involved in breast tumorigenesis

Cited by 37 publications

References 63 publications

SETDB1 induces epithelial‑mesenchymal transition in breast carcinoma by directly binding with Snail promoter

SETDB1 induces epithelial‑mesenchymal transition in breast carcinoma by directly binding with Snail promoter

LncRNA FENDRR represses proliferation, migration and invasion through suppression of survivin in cholangiocarcinoma cells

Epigenetic regulation of epithelial–mesenchymal transition

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