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上皮-间质转化因子ZEB2在卵巢癌中的作用及预后意义

Role and prognostic significance of the epithelial-mesenchymal transition factor ZEB2 in ovarian cancer.

作者信息

Prislei Silvia, Martinelli Enrica, Zannoni Gian Franco, Petrillo Marco, Filippetti Flavia, Mariani Marisa, Mozzetti Simona, Raspaglio Giuseppina, Scambia Giovanni, Ferlini Cristiano

机构信息

Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.

Department of Pathology, Catholic University of the Sacred Heart, Rome, Italy.

出版信息

Oncotarget. 2015 Aug 7;6(22):18966-79. doi: 10.18632/oncotarget.3943.

DOI:10.18632/oncotarget.3943
PMID:26136338
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4662468/
Abstract

ZEB2 is a key factor in epithelial-mesenchymal transition (EMT), a program controlling cell migration in embryonic development and adult tissue homeostasis. We demonstrated a role of ZEB2 in migration and anchorage-independent cell growth in ovarian cancer, as shown by ZEB2 silencing. We found that the RNA-binding protein HuR bound the 3'UTR of ZEB2 mRNA, acting as a positive regulator of ZEB2 protein expression. In Hey ovarian cell line, HuR silencing decreased ZEB2 and ZEB1 nuclear expression and impaired migration. In hypoglycemic conditions ZEB2 expression decreased, along with ZEB1, vimentin and cytoplasmic HuR, and a reduced cellular migration ability was observed. Analysis of ZEB2 and HuR expression in ovarian cancers revealed that nuclear ZEB2 is localized in tumor leading edge and co-localizes with cytoplasmic HuR. In a series of 143 ovarian cancer patients high expression of ZEB2 mRNA significantly correlated with a poor prognosis in term of both overall survival and progression- free survival. Moreover, at immunohistochemical evaluation, we found that prognostic significance of ZEB2 protein relies on its nuclear expression and co-localization with cytoplasmic HuR. In conclusion our findings indicated that nuclear ZEB2 may enhance progression of EMT transition and acquisition of an aggressive phenotype in ovarian cancer.

摘要

ZEB2是上皮-间质转化（EMT）中的关键因子，EMT是一个在胚胎发育和成人组织稳态中控制细胞迁移的程序。我们通过ZEB2沉默证明了ZEB2在卵巢癌细胞迁移和非锚定依赖性生长中的作用。我们发现RNA结合蛋白HuR结合ZEB2 mRNA的3'UTR，作为ZEB2蛋白表达的正调节因子。在Hey卵巢癌细胞系中，HuR沉默降低了ZEB2和ZEB1的核表达并损害了细胞迁移。在低血糖条件下，ZEB2表达下降，同时ZEB1、波形蛋白和细胞质HuR也下降，并且观察到细胞迁移能力降低。对卵巢癌中ZEB2和HuR表达的分析表明，核ZEB2定位于肿瘤前沿并与细胞质HuR共定位。在143例卵巢癌患者中，ZEB2 mRNA的高表达在总生存期和无进展生存期方面均与不良预后显著相关。此外，在免疫组织化学评估中，我们发现ZEB2蛋白的预后意义依赖于其核表达以及与细胞质HuR的共定位。总之，我们的研究结果表明，核ZEB2可能会促进卵巢癌中EMT转化的进程以及侵袭性表型的获得。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ca5/4662468/3d623cf2190c/oncotarget-06-18966-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ca5/4662468/53a35d736878/oncotarget-06-18966-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ca5/4662468/2f13222725ca/oncotarget-06-18966-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ca5/4662468/3d623cf2190c/oncotarget-06-18966-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ca5/4662468/c37bbf5f01f0/oncotarget-06-18966-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ca5/4662468/018639792173/oncotarget-06-18966-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ca5/4662468/245513867bf6/oncotarget-06-18966-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ca5/4662468/b91237e29f2a/oncotarget-06-18966-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ca5/4662468/53a35d736878/oncotarget-06-18966-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ca5/4662468/2f13222725ca/oncotarget-06-18966-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ca5/4662468/3d623cf2190c/oncotarget-06-18966-g007.jpg

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1
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Clin Cancer Res. 2015 Mar 1;21(5):962-968. doi: 10.1158/1078-0432.CCR-13-3173. Epub 2014 Aug 8.
2
Oncogenic roles of EMT-inducing transcription factors.EMT 诱导转录因子的致癌作用。
Nat Cell Biol. 2014 Jun;16(6):488-94. doi: 10.1038/ncb2976.
3
MicroRNA-335 inhibits invasion and metastasis of colorectal cancer by targeting ZEB2.微小RNA-335通过靶向锌指E盒结合蛋白2抑制结直肠癌的侵袭和转移。
锌指E盒结合同源框蛋白2作为多种癌症的预后生物标志物及其与卵巢癌浸润性免疫细胞的相关性
Curr Issues Mol Biol. 2022 Mar 1;44(3):1203-1214. doi: 10.3390/cimb44030079.
4
Prognostic Value of Chemotherapy Response Score (CRS) Assessed on the Adnexa in Ovarian High-Grade Serous Carcinoma: A Systematic Review and Meta-Analysis.附件评估的化疗反应评分（CRS）对卵巢高级别浆液性癌的预后价值：一项系统评价和荟萃分析
Diagnostics (Basel). 2022 Mar 4;12(3):633. doi: 10.3390/diagnostics12030633.
5
Aberrant Methylation of 20 miRNA Genes Specifically Involved in Various Steps of Ovarian Carcinoma Spread: From Primary Tumors to Peritoneal Macroscopic Metastases.20 个 miRNA 基因在卵巢癌扩散的各个步骤中的异常甲基化：从原发性肿瘤到腹膜宏观转移。
Int J Mol Sci. 2022 Jan 24;23(3):1300. doi: 10.3390/ijms23031300.
6
The antitumor effect of miR-448 in epithelial ovarian cancer.miR-448在上皮性卵巢癌中的抗肿瘤作用。
Transl Cancer Res. 2020 Aug;9(8):4922-4930. doi: 10.21037/tcr-20-2464.
7
Evolution of the Neocortex Through RNA-Binding Proteins and Post-transcriptional Regulation.通过RNA结合蛋白和转录后调控看新皮质的进化
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8
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9
RNA-binding proteins in ovarian cancer: a novel avenue of their roles in diagnosis and treatment.RNA 结合蛋白在卵巢癌中的作用：其在诊断和治疗中的新途径。
J Transl Med. 2022 Jan 21;20(1):37. doi: 10.1186/s12967-022-03245-6.
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Med Oncol. 2014 Jun;31(6):982. doi: 10.1007/s12032-014-0982-8. Epub 2014 May 15.
4
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5
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6
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7
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8
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Carcinogenesis. 2013 Oct;34(10):2231-9. doi: 10.1093/carcin/bgt184. Epub 2013 May 28.
9
Protein expression of ZEB2 in renal cell carcinoma and its prognostic significance in patient survival.肾细胞癌中 ZEB2 的蛋白表达及其对患者生存预后的意义。
PLoS One. 2013 May 2;8(5):e62558. doi: 10.1371/journal.pone.0062558. Print 2013.
10
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Oncogene. 2014 Mar 6;33(10):1325-35. doi: 10.1038/onc.2013.53. Epub 2013 Mar 11.