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EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer.

ABSTRACT: Enhancer of zeste homolog 2 (EZH2) is an essential component of the polycomb repressive complex 2 (PRC2), which is required for epigenetic silencing of target genes, including those affecting cancer progression. Its role in pancreatic cancer remains to be clarified; therefore, we investigated the effects of aberrantly expressed EZH2 on pancreatic cancer. We found that EZH2 expression is up-regulated in pancreatic cancer tissues and positively correlated with lymph node metastasis and advanced clinical stage in pancreatic cancer patients. EZH2 knockdown in pancreatic cancer cell lines inhibited cell migration and invasion, but did not alter cell proliferation. Silencing of EZH2 also increased E-cadherin expression in vitro, and E-cadherin expression was inversely correlated with EZH2 expression in pancreatic cancer tissue samples. Patients with high EZH2 and low E-cadherin expression had the worst prognosis. RIP and ChIP assays suggest that EZH2 is recruited to the E-cadherin promoter by the long non-coding RNA, MALAT-1 (metastasis associated in lung adenocarcinoma transcript 1), where it represses E-cadherin expression. Our results show that EZH2-based therapies may be an option for the treatment of pancreatic cancer.

SUBMITTER: Han T

PROVIDER: S-EPMC4905466 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer.

Han Ting T Jiao Feng F Hu Hai H Yuan Cuncun C Wang Lei L Jin Zi-Liang ZL Song Wei-Feng WF Wang Li-Wei LW

Oncotarget 20160301 10

Enhancer of zeste homolog 2 (EZH2) is an essential component of the polycomb repressive complex 2 (PRC2), which is required for epigenetic silencing of target genes, including those affecting cancer progression. Its role in pancreatic cancer remains to be clarified; therefore, we investigated the effects of aberrantly expressed EZH2 on pancreatic cancer. We found that EZH2 expression is up-regulated in pancreatic cancer tissues and positively correlated with lymph node metastasis and advanced cl ...[more]

PMID: 26848980

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Project description:circRNAs have been demonstrated to be key regulators of bladder cancer progression. The present study aimed to investigate the effects of circular RNA (circ)_0067934 in bladder cancer progression. A total of 54 patients with primary bladder cancer were enrolled, and their tumor tissues and adjacent normal bladder tissues were collected. For in vitro functional assays, T24 cells were transfected with sicirc_0067934, and Cell Counting Kit-8 was used to analyze the proliferative capacity of T24 cells. In addition, Transwell and Matrigel assays were used to assess the cell migration and invasion abilities, and a dual-luciferase reporter assay was used to investigate the relationship between miR-1304 and circ_0067934. Finally, reverse transcription-quantitative PCR and western blotting were performed to analyze gene and protein expression levels, respectively. circ_0067934 expression levels were significantly increased in bladder cancer tissues (P<0.001), which was associated with metastasis and a significantly decreased 5-year overall (P<0.05) and disease-free survival (P<0.05). In vitro, T24 cells in the small interfering RNA (si)circ_0067934 group demonstrated significantly reduced proliferation, migration and invasion abilities compared with the si negative control (siNC) group (P<0.01). In addition, the knockdown of circ_0067934 directly increased microRNA (miR)-1304 expression levels in T24 cells. Myc was subsequently discovered to be directly inhibited by miR-1304 and circ_0067934 was observed to increase Myc expression levels in T24 cells through inhibiting miR-1304 expression levels (P<0.01). Compared with the siNC group and sicirc_0067934 + Myc overexpression group, T24 cells in the sicirc_0067934 group exhibited significantly decreased proliferative, migratory and invasive abilities (P<0.01). In conclusion, circ_0067934 was demonstrated to increase bladder cancer cell proliferation, migration and invasion through promoting Myc expression levels via the suppression of miR-1304 expression.

Dataset Information

EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer.

Publications

EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer.

Similar Datasets

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