A novel miR-193a-5p-YY1-APC regulatory axis in human endometrioid endometrial adenocarcinoma
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摘要Aberrant expression and altered function of transcription factors (TFs) have vital roles in many aspects of tumor development and progression. In this study, we investigated the functional significance of a TF, Yin Yang1 (YY1) in tumorigenesis of endometrioid endometrial carcinoma (EEC). We demonstrated that YY1 is upregulated in EEC cell lines and primary tumors; and its expression is associated with tumor stages. Depletion of YY1 inhibits EEC cell proliferation and migration both in vitro and in vivo, whereas overexpression of YY1 promotes EEC cell growth. These results suggest that YY1 functions as an oncogenic factor in EEC. Transcriptome analysis revealed a significant effect of YY1 on critical aspects of EEC tumorigenesis through inhibition of APC expression. Further mechanistic investigation uncovered a new epigenetic silencing mode of APC by YY1 through recruitment of EZH2 and trimethylation of histone 3 lysine 27 on its promoter region. Moreover, YY1 overexpression was found to be a consequence of miR-193a-5p downregulation through direct miR-193a-5p-YY1 interplay. Our results therefore establish a novel miR-193a-5p-YY1-APC axis, which contributes to EEC development, and may serve as future intervention target.
著者Yang Y, Zhou L, Lu L, Wang L, Li X, Jiang P, Chan LKY, Zhang T, Yu J, Kwong J, Cheung T, Chung T, Mak K, Sun H, Wang H
期刊名稱Oncogene
詳細描述To ORKTS: Duplicate record P125310 and P120348 deleted.
出版年份2013
月份7
日期18
卷號32
期次29
出版社Nature Publishing Group: Open Access Hybrid Model Option B
頁次3432 - 3442
國際標準期刊號0950-9232
電子國際標準期刊號1476-5594
語言英式英語
關鍵詞APC; EEC; EZH2; H3K27me3; microRNA; YY1
Web of Science 學科類別Biochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY; Genetics & Heredity; GENETICS & HEREDITY; Oncology; ONCOLOGY

上次更新時間 2020-30-11 於 23:41