<i>Retracted</i>: Role of <scp>STAT3</scp> and vitamin D receptor in <i>EZH2</i>‐mediated invasion of human colorectal cancer

Yan, Lin; Ren, Lin; Xiong, Hua; Du, Wei; Yu, You; Sun, Tian; Weng, Yu; Wang, Zhen Hua; Wang, Jilin; Wang, Ying Chao; Cui, Yun; Sun, Dan; Han, Ze‐Guang; Shen, Nan; Zou, Weiping; Xu, Jie; Chen, Hao Yan; Cao, Weibiao; Hong, Jie; Fang, Jing

doi:10.1002/path.4179

Cited by 36 publications

(28 citation statements)

References 42 publications

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“…P-STAT3 has been show to upregulate EZH2 expression in colorectal cancer. 12,13 We found that none of the aggressive B-cell lymphomas studied showed significant p-STAT3 positivity in neoplastic cells (o 10% cell positivity), suggesting that it may not have a significant role in EZH2 overexpression in aggressive B-cell lymphomas.…”

Section: Discussionmentioning

confidence: 77%

“…9 In colorectal carcinoma, STAT3 is constitutively activated, directly binds to the EZH2 promoter, and regulates its expression, which is thought to contribute to colon cancer development and metastasis. [10][11][12][13] Recent evidence supports a more complicated mechanism of EZH2's contribution to tumor development in hematopoietic malignancies. Hyperactivation of polycomb group proteins, particularly EZH2, has been linked to the pathogenesis of a subset of hematological malignancies, including some B-and T-cell lymphomas as well as myeloid disorders.…”

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confidence: 99%

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Differential expression of enhancer of zeste homolog 2 (EZH2) protein in small cell and aggressive B-cell non-Hodgkin lymphomas and differential regulation of EZH2 expression by p-ERK1/2 and MYC in aggressive B-cell lymphomas

et al. 2016

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EZH2, a member of the polycomb protein group, is an important methyltransferase that is overexpressed in various neoplasms. We found that in small cell B-cell lymphomas, EZH2 is expressed in o 40% of neoplastic cells, with heterogenous signal intensity. In aggressive B-cell lymphomas, 70-100% of tumor cells were positive for EZH2 expression with high signal intensity, which correlated with a high proliferation rate. We investigated the potential signaling molecules that regulate EZH2 overexpression in aggressive B-cell lymphomas and found that 80% of cases of EZH2-positive diffuse large B-cell lymphoma show high p-ERK1/2 expression (average~57% tumor cell positivity). In contrast, only a small percentage of tumor cells (~10%) show p-ERK1/2 expression in Burkitt lymphoma and double hit lymphoma. On average, 91 and 76% of neoplastic cells were positive for MYC expression in Burkitt lymphoma and double hit lymphoma, respectively, while only 20% neoplastic cells were positive for MYC expression in diffuse large B-cell lymphoma. None of the aggressive B-cell lymphomas showed significant p-STAT3 expression in EZH2-overexpressed cases. The correlation of EZH2 expression with aggressive behavior and proliferation rate in B-cell neoplasms suggests that this molecule may function as an oncogenic protein in these neoplasms, with possible regulation by different signaling cascades in different types of aggressive B-cell lymphomas: p-ERK-related signaling in diffuse large B-cell lymphoma, and MYC-related signaling in Burkitt lymphoma and double hit lymphoma. Furthermore, EZH2 and associated signaling cascades may serve as therapeutic targets for the treatment of aggressive B-cell lymphomas. EZH2 is an important enzymatic subunit of the epigenetic regulator polycomb repressive complex 2 (PRC2) and functions as a methytransferase that targets the lysine 27 of histone H3 and controls gene silencing through posttranslational modification. 1 EZH2 is frequently overexpressed in various nonhematological malignancies and functions as an oncogenic protein for tumor cell proliferation, metastasis, and survival. 2 A number of intracytoplasmic oncogenic signaling molecules, transcription factors, and tumor-suppressor miRNAs regulate EZH2 expression in these non-hematological neoplasms. In the triple-negative and ERBB2-overexpressing aggressive subtypes of breast cancer, studies using promoter analysis and in vitro inhibitor methods demonstrated that the MEK/ERK/Elk-1 signaling pathway leads to EZH2 overexpression. 3 In a subset of invasive breast carcinomas and moderately to poorly differentiated non-small cell lung cancers, AKT(Ser473) phosphorylation was closely associated with EZH2 overexpression. 4,5 In prostate and hepatocellular carcinomas, upregulation of MYC protein results in the overexpression of EZH2 through reduction of miR-26a, miR26b, and miR-101. In addition, MYC can directly bind to and activate the EZH2 promoter. [6][7][8]

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Section: Discussionmentioning

confidence: 77%

mentioning

confidence: 99%

Differential expression of enhancer of zeste homolog 2 (EZH2) protein in small cell and aggressive B-cell non-Hodgkin lymphomas and differential regulation of EZH2 expression by p-ERK1/2 and MYC in aggressive B-cell lymphomas

et al. 2016

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“…HIC-1 is a multifunctional, sequence-specific transcriptional repressor that interacts with several major repression and chromatin remodeling complexes [42, 43]. To date, many studies have showed that the IL-6/Janus kinase/STAT3 signaling pathways are involved in drug resistance, angiogenesis, migration, and other processes in cancers [44, 45]. IL-6-induced transcriptional factor or cytokines, such as c-Myc and vascular endothelial growth factor, initiate and promote cell growth by triggering proliferation, and MMP2 and MMP9 proteins induce cell migration, which is closely related to metastasis and invasiveness in human cancer [46, 47].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of hypermethylated in cancer-1 by miR-4532 promotes adriamycin resistance in breast cancer cells

et al. 2018

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BackgroundMicroRNAs are small RNAs (~ 22 nt) that modulate the expression of thousands of genes in tumors and play important roles in the formation of multidrug resistance. In this study, we firstly investigated that miR-4532 involved in the multidrug resistance formation of breast cancer by targeting hypermethylated in cancer 1 (HIC-1), a tumor-suppressor gene.MethodsTo identify and characterize the possible miRNAs in regulating multidrug resistance, we employed the transcriptome sequencing approach to profile the changes in the expression of miRNAs and their target mRNAs were obtained by bioinformatics prediction. Then the molecular biology experiments were conducted to confirm miR-4532 involved in multidrug resistance formation of breast cancer.ResultsThe luciferase reporter assay experiment was employed to confirm that HIC-1 was the target of miR-4532. Transfection with an miR-4532 mimic indicated miR-4532 mimic significantly increased breast cancer cell resistance to adriamycin. Cell proliferation and invasion assay experiments showed overexpression of HIC-1 inhibited the invasion and metastasis of breast cancer cells. Meanwhile, the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway was confirmed to be involving in multidrug resistance by western blotting experiments.ConclusionsThese results suggest that downregulation of hypermethylated in cancer-1 by miR-4532 could promote adriamycin resistance in breast cancer cells, in which the IL-6/STAT3 pathway was regulated by the HIC-1. This finding might contribute to new therapeutic target for reversal of tumor resistance.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0616-x) contains supplementary material, which is available to authorized users.

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“…28 Now we have analyzed the ChIP sequencing data and found that STAT3 has several binding sites in the promoters of SUZ12 and EED. In support of this, STAT3 can directly bind to the promoter of SUZ12 and EED, regulating their expression.…”

Section: Discussionmentioning

confidence: 99%

Th22 cells control colon tumorigenesis through STAT3 and Polycomb Repression complex 2 signaling

et al. 2015

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Th22 cells traffic to and retain in the colon cancer microenvironment, and target core stem cell genes and promote colon cancer stemness via STAT3 and H3K79me2 signaling pathway and contribute to colon carcinogenesis. However, whether Th22 cells affect colon cancer cell proliferation and apoptosis remains unknown. We studied the interaction between Th22 cells and colon cancer cells in the colon cancer microenvironment. Colon cancer proliferation was examined by flow cytometry analysis and H 3 thymidine incorporation. Cell cycle related genes were quantified by real-time PCR and Western blotting. We transfected colon cancer cells with lentiviral vector encoding specific gene shRNAs and used chromatin immunoprecipitation (ChIP) assay to determine the genetic signaling involved in interleukin (IL)-22-mediated colon cancer cell proliferation. We showed that Th22 cells released IL-22 and stimulated colon cancer proliferation. Mechanistically, IL-22 activated STAT3, and subsequently STAT3 bound to the promoter areas of the Polycomb Repression complex 2 (PRC2) components SUZ12 and EED, and stimulated the expression of PRC2. Consequently, the activated PRC2 catalyzed the promoters of the cell cycle check-point genes p16 and p21, and inhibited their expression through H3K27me3-mediated histone methylation, and ultimately caused colon cancer cell proliferation. Bioinformatics analysis revealed that the levels of IL-22 expression positively correlated with the levels of genes controlling cancer proliferation and cell cycling in colon cancer. In addition to controlling colon cancer stemness, Th22 cells support colon carcinogenesis via affecting colon cancer cell proliferation through a distinct histone modification.

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Retracted: Role of STAT3 and vitamin D receptor in EZH2‐mediated invasion of human colorectal cancer

Cited by 36 publications

References 42 publications

Differential expression of enhancer of zeste homolog 2 (EZH2) protein in small cell and aggressive B-cell non-Hodgkin lymphomas and differential regulation of EZH2 expression by p-ERK1/2 and MYC in aggressive B-cell lymphomas

Differential expression of enhancer of zeste homolog 2 (EZH2) protein in small cell and aggressive B-cell non-Hodgkin lymphomas and differential regulation of EZH2 expression by p-ERK1/2 and MYC in aggressive B-cell lymphomas

Downregulation of hypermethylated in cancer-1 by miR-4532 promotes adriamycin resistance in breast cancer cells

Th22 cells control colon tumorigenesis through STAT3 and Polycomb Repression complex 2 signaling

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