They demonstrated that ZRANB1 can bind , deubiquitinate , and stabilize EZH2 , which enhances breast cancer tumorigenesis and metastasis .

For instance , EZH2 can promote the invasion and metastasis by suppressing E-cadherin transcriptional expression [ 28 , 29 ] ; EZH2 can also increase tumorigenesis by silencing tumor suppressors [ 9 , 20 , 25 ] .

Whether EZH2 acts to repress or stimulate transcription largely relates to its association with other proteins .

There are three potential mechanisms to explain these paradoxical findings : ( 1 ) Oxidative stress can induce EZH2 expression by additional mechanisms independent of our suggested mTORC1 / glycolysis / miRNA axis ; ( 2 ) A negative feedback homeostasis loop may exist to suppress EZH2 via miR-26a and miR-101 as EZH2 levels were significantly increased about 40 folds with oxidative stress ; and ( 3 ) miR-26a and miR-101 could be directly regulated by oxidative stress independent of mTORC1 / glycolysis .

These results suggest that oxidative stress upregulated EZH2 expression , via mechanisms that might be independent of post-transcriptional regulation by miR-26a and miR-101 .

Increased EZH2 is mediated by activation of mTORC1 and increased glycolysis in SLE CD4 + T cells .

Conclusion : Increased EZH2 is mediated by activation of mTORC1 and increased glycolysis in SLE CD4 + T cells .

Because mTORC1 is activated in SLE CD4 + T cells in part due to increased oxidative stress , and mTORC1 activation increases glycolysis , we hypothesized that mTORC1 mediates increased EZH2 expression .

Because mTORC1 is activated in SLE CD4 + T cells in part due to increased oxidative stress , and mTORC1 activation increases glycolysis , we hypothesized that mTORC1 mediates increased EZH2 expression .

On the contrary , Nanog suppresses p53 activity while Gli activated by Nanog inhibits p53 by activating Mdm2 to promote pluripotency .

For example , p53 repress CD133 by directly binding to its promoter and recruiting HDAC1 ( Figure 2 ) .

p53 loss upregulates CD133 which subsequently promotes CSC marker expression and confers stemness .

With the advent of reprogramming era , it was further highlighted that p53 loss promote dedifferentiation and reprogramming under favorable conditions .

Also , upon DNA damage , p53 primarily promotes differentiation by suppression of Nanog .

Further , induction of miR-34a by p53 functionally targets the CSC marker CD44 , thereby inhibiting prostate cancer regeneration and metastasis ( Figure 2 ) ( 74 ) .

Additionally , p53 upregulates miR-34a that represses Notch ( Figure 2 ) and anti-apoptotic Bcl2 thereby promoting differentiation and apoptosis ( 82 ) .

Inactivation of p53 disrupts this balance and promotes pluripotency and somatic cell reprogramming .

Inactivation of p53 disrupts this balance and promotes pluripotency and somatic cell reprogramming .

Similarly , p53 activation by nutlin leads to transcriptional activation of p21 that cause cell cycle arrest and induces differentiation in human ESCs ( 35 ) .

EZH2 knockdown reduces CSCs and inhibits chemoresistance and tumorigenesis in ovarian cancer cells To examine the effect of EZH2 on CSC populations in ovarian cancer , we first compared the protein level of EZH2 in SKOV3 , SK-1st , SK-2nd and SK-3rd cells by Western blot and found a gradual increase in the EZH2 level ( Figure 2A ) .

EZH2 knockdown reduces CSCs and inhibits chemoresistance and tumorigenesis in ovarian cancer cells To examine the effect of EZH2 on CSC populations in ovarian cancer , we first compared the protein level of EZH2 in SKOV3 , SK-1st , SK-2nd and SK-3rd cells by Western blot and found a gradual increase in the EZH2 level ( Figure 2A ) .

In addition , it was reported that EZH2 knockdown significantly reduces the frequency of CSCs in pancreatic ductal adenocarcinoma 38 .

Conclusions : Our data revealed a previously unidentified functional and mechanistic link between EZH2 levels , CHK1 signaling activation , and ovarian CSCs and provided strong evidence that EZH2 promotes ovarian cancer chemoresistance and recurrence .

Conclusions : Our data revealed a previously unidentified functional and mechanistic link between EZH2 levels , CHK1 signaling activation , and ovarian CSCs and provided strong evidence that EZH2 promotes ovarian cancer chemoresistance and recurrence .

In our study , we uncovered a mechanism by which EZH2 directly occupies the promoter region of CHK1 and induces its activation in epithelial ovarian cancer , which is consistent with a recent study showing that EZH2 functioned in activating NOTCH1 signaling by directly binding to the NOTCH1 promoter in breast cancer 37 .

EZH2 activates CHK1 signaling to promote ovarian cancer chemoresistance by maintaining the properties of cancer stem cells Background : Ovarian cancer is a fatal malignant gynecological tumor .

A luciferase reporter assay and chromatin immunoprecipitation assay were performed to identify activation of CHK1 by EZH2 .

A luciferase reporter assay and chromatin immunoprecipitation assay were performed to identify activation of CHK1 by EZH2 .

EZH2 transcriptionally upregulates CHK1 expression by directly binding to the CHK1 promoter , and inhibition of CHK1abrogates G2 / M checkpoints and promotes DNA damaging agent-induced cell death in EOCSC .

In addition , ChIP assays showed that EZH2 bound directly to region 1 and region 2 within the CHK1 promoter region in both SKOV3 and A2780 cells ( Figure 3F-H ) , indicating that EZH2 upregulated CHK1 expression by targeting the CHK1 promoter .

The protein expression studies have further revealed that vanillin reduces the CDK6 expression and induces apoptosis in the cancer cells .

Enzyme inhibition and fluorescence-binding studies showed that vanillin inhibits CDK6 with an half maximal inhibitory concentration = 4.99 muM and a binding constant ( K ) 4.1 x 10 7 M -1 .

On the contrary , Nanog suppresses p53 activity while Gli activated by Nanog inhibits p53 by activating Mdm2 to promote pluripotency .

For example , p53 repress CD133 by directly binding to its promoter and recruiting HDAC1 ( Figure 2 ) .

p53 loss upregulates CD133 which subsequently promotes CSC marker expression and confers stemness .

With the advent of reprogramming era , it was further highlighted that p53 loss promote dedifferentiation and reprogramming under favorable conditions .

Also , upon DNA damage , p53 primarily promotes differentiation by suppression of Nanog .

Additionally , p53 upregulates miR-34a that represses Notch ( Figure 2 ) and anti-apoptotic Bcl2 thereby promoting differentiation and apoptosis ( 82 ) .

Further , induction of miR-34a by p53 functionally targets the CSC marker CD44 , thereby inhibiting prostate cancer regeneration and metastasis ( Figure 2 ) ( 74 ) .

Inactivation of p53 disrupts this balance and promotes pluripotency and somatic cell reprogramming .

Inactivation of p53 disrupts this balance and promotes pluripotency and somatic cell reprogramming .

Similarly , p53 activation by nutlin leads to transcriptional activation of p21 that cause cell cycle arrest and induces differentiation in human ESCs ( 35 ) .

There are three potential mechanisms to explain these paradoxical findings : ( 1 ) Oxidative stress can induce EZH2 expression by additional mechanisms independent of our suggested mTORC1 / glycolysis / miRNA axis ; ( 2 ) A negative feedback homeostasis loop may exist to suppress EZH2 via miR-26a and miR-101 as EZH2 levels were significantly increased about 40 folds with oxidative stress ; and ( 3 ) miR-26a and miR-101 could be directly regulated by oxidative stress independent of mTORC1 / glycolysis .

These results suggest that oxidative stress upregulated EZH2 expression , via mechanisms that might be independent of post-transcriptional regulation by miR-26a and miR-101 .

Conclusion : Increased EZH2 is mediated by activation of mTORC1 and increased glycolysis in SLE CD4 + T cells .

Increased EZH2 is mediated by activation of mTORC1 and increased glycolysis in SLE CD4 + T cells .

Because mTORC1 is activated in SLE CD4 + T cells in part due to increased oxidative stress , and mTORC1 activation increases glycolysis , we hypothesized that mTORC1 mediates increased EZH2 expression .

Because mTORC1 is activated in SLE CD4 + T cells in part due to increased oxidative stress , and mTORC1 activation increases glycolysis , we hypothesized that mTORC1 mediates increased EZH2 expression .

Moreover , Jin et al. [ 50 ] revealed that FBW7 decreases EZH2 activity and attenuates the motility of pancreatic cancer cells by mediating the degradation of the EZH2 ubiquitin proteasome pathway .

Recently , a report has confirmed that Praja1 degrades EZH2 during skeletal myogenesis [ 38 ] .

Aaron and his colleagues illustrated that Praja1 promotes EZH2 degradation through K48-linkage polyubiquitination and suppresses cells growth and migration in breast cancer [ 87 ] .

A recent research has disclosed that sorafenib can prevent EZH2 expression by accelerating its ubiquitination-proteasome degradation in hepatoma cells [ 117 ] .

For instance , EZH2 can promote the invasion and metastasis by suppressing E-cadherin transcriptional expression [ 28 , 29 ] ; EZH2 can also increase tumorigenesis by silencing tumor suppressors [ 9 , 20 , 25 ] .

It means that EZH2 can activate gene expression and oncogenesis without being dependent on its methyltransferase activity .

For instance , EZH2 can promote the invasion and metastasis by suppressing E-cadherin transcriptional expression [ 28 , 29 ] ; EZH2 can also increase tumorigenesis by silencing tumor suppressors [ 9 , 20 , 25 ] .

EZH2 reportedly promotes cancer development and metastasis [ 9 , 17 , 18 ] .

They demonstrated that ZRANB1 can bind , deubiquitinate , and stabilize EZH2 , which enhances breast cancer tumorigenesis and metastasis .

For instance , EZH2 can promote the invasion and metastasis by suppressing E-cadherin transcriptional expression [ 28 , 29 ] ; EZH2 can also increase tumorigenesis by silencing tumor suppressors [ 9 , 20 , 25 ] .

Dissecting the functional roles of Trio and Myh9 in NCCs Because directional migration depends on the activation of small GTPases at the leading edge of cell protrusions and because Trio is a well-known GEF that likely acts upstream of the small GTPase family 31 , 32 , we evaluated whether Trio activated Rac1 and Cdc42 in NCC migration .

In this study , knockdown of EZH2 significantly inhibited TNBC cell proliferation and impaired cell migration and invasion , whereas overexpression of EZH2 produced an inverse phenotype .

Functionally , DDX11 promoted cell proliferation by inducing the expression of EZH2 , a famous oncogene ( 20 , 25 ) , to subsequently inhibit the expression of p21 , a well-known tumor suppressor .

Functionally , DDX11 promoted cell proliferation by inducing the expression of EZH2 , a famous oncogene ( 20 , 25 ) , to subsequently inhibit the expression of p21 , a well-known tumor suppressor .