The degradation of EZH2 mediated by lncRNA ANCR attenuated the invasion and metastasis of breast cancer

Li, Zhongwei; Hou, Pingfu; Fan, Daiming; Dong, Meichen; Ma, Musong; Li, Hongyuan; Yao, Ruosi; Li, Yuxin; Wang, Guannan; Geng, Pengyu; Mihretab, Adhanom; Li, Dongxu; Zhang, Yu; Huang, Baiqu; Lü, Jun

doi:10.1038/cdd.2016.95

Cited by 285 publications

(242 citation statements)

References 54 publications

(72 reference statements)

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“…Therefore, by performing RIP assays we demonstrated that PAR5 directly binds EZH2. Moreover, we observed that PAR5 restoration reduced EZH2 protein and H3K27me3 levels in absence of any change of EZH2 mRNA abundance, suggesting that this lncRNA may affect EZH2 stability by a regulatory mechanism already reported for other lncRNAs [32,33]. Consistently with these findings, we found an increased EZH2 expression in ATC tissues and, interestingly, we observed a negative correlation between EZH2 protein and PAR5 RNA levels, strongly supporting the effects of PAR5 on EZH2.…”

Section: Discussionsupporting

confidence: 90%

The Long Non-Coding RNA Prader Willi/Angelman Region RNA5 (PAR5) Is Downregulated in Anaplastic Thyroid Carcinomas Where It Acts as a Tumor Suppressor by Reducing EZH2 Activity

Pellecchia

Sepe

Decaussin‐Petrucci

et al. 2020

Cancers

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Anaplastic thyroid carcinoma (ATC) represents one the most aggressive neoplasias in humans, and, nowadays, limited advances have been made to extend the survival and reduce the mortality of ATC. Thus, the identification of molecular mechanism underlying its progression is needed. Here, we evaluated the long non-coding RNA (lncRNA) expression profile of nine ATC in comparison with five normal thyroid tissues by a lncRNA microarray. By this analysis, we identified 19 upregulated and 28 downregulated lncRNAs with a fold change >1.1 or <−1.1 and p-value < 0.05, in ATC samples. Some of them were subsequently validated by qRT-PCR. Then, we investigated the role of the lncRNA Prader Willi/Angelman region RNA5 (PAR5), drastically and specifically downregulated in ATC. The restoration of PAR5 reduces proliferation and migration rates of ATC-derived cell lines indicating that its downregulation contributes to thyroid cancer progression. Our results suggest that PAR5 exerts its anti-oncogenic role by impairing Enhancer of Zeste Homolog 2 (EZH2) oncogenic activity since we demonstrated that PAR5 interacts with it in thyroid cancer cell lines, reducing EZH2 protein levels and its binding on the E-cadherin promoter, relieving E-cadherin from the negative regulation by EZH2. Consistently, EZH2 is overexpressed in ATC, but not in differentiated thyroid carcinomas. The results reported here define a tumor suppressor role for PAR5 in undifferentiated thyroid neoplasias, further highlighting the pivotal role of lncRNAs in thyroid carcinogenesis.

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Section: Discussionsupporting

confidence: 90%

The Long Non-Coding RNA Prader Willi/Angelman Region RNA5 (PAR5) Is Downregulated in Anaplastic Thyroid Carcinomas Where It Acts as a Tumor Suppressor by Reducing EZH2 Activity

Pellecchia

Sepe

Decaussin‐Petrucci

et al. 2020

Cancers

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“…Recently, the potential role of DANCR in cancer has been reported in several studies; however, these studies showed that DANCR plays opposite roles depending on the tumour type. In colorectal cancer, hepatocellular carcinoma and prostate cancer, DANCR functions as an oncogene; on the contrary, another report indicated that DANCR functions as a tumour suppressor in breast cancer via degrading the epigenetic tumour regulator EZH2 [13][14][15][16]. This phenomenon may explain the variable expression and biological patterns of DANCR in different cancer types.…”

Section: Discussionmentioning

confidence: 98%

LncRNA‐DANCR contributes to lung adenocarcinoma progression by sponging miR‐496 to modulate mTOR expression

Rui

Guo

et al. 2017

J Cellular Molecular Medi

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Long non‐coding RNAs (lncRNAs) have emerged as new and important regulators of pathological processes including tumour development. In this study, we demonstrated that differentiation antagonizing non‐protein coding RNA (DANCR) was up‐regulated in lung adenocarcinoma (ADC) and that the knockdown of DANCR inhibited tumour cell proliferation, migration and invasion and restored cell apoptosis rescued; cotransfection with a miR‐496 inhibitor reversed these effects. Luciferase reporter assays showed that miR‐496 directly modulated DANCR; additionally, we used RNA‐binding protein immunoprecipitation (RIP) and RNA pull‐down assays to further confirm that the suppression of DANCR by miR‐496 was RISC‐dependent. Our study also indicated that mTOR was a target of miR‐496 and that DANCR could modulate the expression levels of mTOR by working as a competing endogenous RNA (ceRNA). Furthermore, the knockdown of DANCR reduced tumour volumes in vivo compared with those of the control group. In conclusion, this study showed that DANCR might be an oncogenic lncRNA that regulates mTOR expression through directly binding to miR‐496. DANCR may be regarded as a biomarker or therapeutic target for ADC.

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“…* p < 0.05; * * p < 0.01. target genes (Gupta et al, 2010). LncRNA ANCR interacts with EZH2 to promote its phosphorylation that facilitates EZH2 degradation and suppresses breast cancer progression (Li et al, 2017). In this study, we demonstrated that LINC-PINT was an EZH2-binding lncRNA and play an tumorsuppressive role in melanoma progression.…”

Section: Discussionmentioning

confidence: 69%

Long Non-coding RNA LINC-PINT Suppresses Cell Proliferation and Migration of Melanoma via Recruiting EZH2

Wang

et al. 2019

Front. Cell Dev. Biol.

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Long non-coding RNAs (lncRNAs) have been identified as crucial regulators in many human cancers. Many lncRNAs show aberrant expression in cancer, and some of them play critical roles in tumor proliferation, invasion, and metastasis. However, the regulatory functions of lncRNAs in melanoma progression remain to be elucidated. We utilized the Real-time PCR methodology to determine the expression of LINC-PINT in melanoma cell lines. To evaluate the effect of LINC-PINT on tumorigenesis of melanoma, we used Cell Counting Kit-8 (CCK8) and colony formation assay. Flow cytometry assay was used to detect the function of LINC-PINT on cell cycle status. PINT-interacting proteins were identified by chromatin isolation using RNA purification (ChIRP). Microarray assay and bioinformatics analysis were used to find the potential target genes of LINC-PINT and the status of LINC-PINT target gene candidate was verified using chromatin immunoprecipitation assay (ChIP). LINC-PINT plays a role in suppressing the tumorigenicity of melanoma, which was further determined by xenograft model assay. LINC-PINT was significantly downregulated in melanoma tissues and cell lines. The overexpression of LINC-PINT in tumor cells resulted in significant tumor growth reduction and migration inhibition in A375, Mum2B and CRMM1 cells. Results based on the in vivo xenograft model were further consistent with the in vitro findings that LINC-PINT impeded growth and metastasis of melanoma cells. Microarray assay and bioinformatics analysis indicated that CDK1, CCNA2, AURKA, and PCNA were potential targets of LINC-PINT. In conclusion, LINC-PINT inhibits the tumorigenicity of melanoma through recruiting EZH2 to the promoter of its target genes, leading to H3K27 trimethylation and epigenetic silencing of target genes. LINC-PINT may serve as a novel diagnostic and therapeutic target for melanoma.

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The degradation of EZH2 mediated by lncRNA ANCR attenuated the invasion and metastasis of breast cancer

Cited by 285 publications

References 54 publications

The Long Non-Coding RNA Prader Willi/Angelman Region RNA5 (PAR5) Is Downregulated in Anaplastic Thyroid Carcinomas Where It Acts as a Tumor Suppressor by Reducing EZH2 Activity

The Long Non-Coding RNA Prader Willi/Angelman Region RNA5 (PAR5) Is Downregulated in Anaplastic Thyroid Carcinomas Where It Acts as a Tumor Suppressor by Reducing EZH2 Activity

LncRNA‐DANCR contributes to lung adenocarcinoma progression by sponging miR‐496 to modulate mTOR expression

Long Non-coding RNA LINC-PINT Suppresses Cell Proliferation and Migration of Melanoma via Recruiting EZH2

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