Reactivation of epigenetically silenced miR-124 reverses the epithelial-to-mesenchymal transition and inhibits invasion in endometrial cancer cells via the direct repression of IQGAP1 expression

Dong, Peixin; Ihira, Kei; Xiong, Ying; Watari, Hidemichi; Hanley, Sharon J.B.; Yamada, Takahiro; Hosaka, Masayoshi; Kudo, Masataka; Yue, Junming; Sakuragi, Noriaki

Reactivation of epigenetically silenced miR-124 reverses the epithelial-to-mesenchymal transition and inhibits invasion in endometrial cancer cells via the direct repression of IQGAP1 expression

Dong, Peixin; Ihira, Kei; Xiong, Ying et al.

Oncotarget, 2016, 7(15), 20260-20270

Permalink : https://hdl.handle.net/2115/61462

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アクセス権	open access
URI	https://hdl.handle.net/2115/61462
タイトル	Reactivation of epigenetically silenced miR-124 reverses the epithelial-to-mesenchymal transition and inhibits invasion in endometrial cancer cells via the direct repression of IQGAP1 expression
著者	Dong, Peixin ; Ihira, Kei ; Xiong, Ying ; Watari, Hidemichi ; Hanley, Sharon J.B. ; Yamada, Takahiro ; Hosaka, Masayoshi ; Kudo, Masataka ; Yue, Junming ; Sakuragi, Noriaki
e-Rad_Researcher 50602504 著者名 Dong, Peixin
著者名 Ihira, Kei
著者名 Xiong, Ying
e-Rad_Researcher 10344508 著者名 Watari, Hidemichi
e-Rad_Researcher 80529412 著者名 Hanley, Sharon J.B.
e-Rad_Researcher 20419948 著者名 Yamada, Takahiro
著者名 Hosaka, Masayoshi
著者名 Kudo, Masataka
著者名 Yue, Junming
e-Rad_Researcher 70153963 著者名 Sakuragi, Noriaki
言語	英語
キーワード	IQGAP1
	miR-124
	endometrial cancer cell invasion
	epigenetics
	DNA methyltransferase inhibitor
発行日	2016-04-12
出版者	Impact Journals
収録物名	Oncotarget
巻(号)	7(15)
ページ	20260-20270
抄録	Overexpression of IQGAP1 and microRNA (miRNA) dysregulation are frequent in human tumors, but little is known about the role of IQGAP1 and its relationship to miRNA in endometrial carcinogenesis. We demonstrate that IQGAP1 activates the epithelial?mesenchymal transition (EMT) program and that miR-124 directly represses IQGAP1 expression in endometrial cancer (EC) cells. The overexpression of IQGAP1 stimulates EMT features and enhances migration, invasion and proliferation of EC cells, whereas knocking down IQGAP1 expression reverses EMT and inhibits these malignant properties. Using miRNA microarray profiling, we identified 29 miRNAs (let-7b, let-7f, miR-10b, miR-15b, miR-23a, miR-24, miR-25, miR-27a, miR-29b, miR-30a-5p, miR-34a, miR-124, miR-127, miR-130b, miR-148a, miR-155, miR-191, miR-194, miR-224, miR-362, miR-409-3p, miR-422b, miR-424, miR-453, miR-497, miR-518d, miR-518f, miR-526a and miR-656) that are significantly down-regulated in an in vitro-selected highly invasive derivative cell line (HEC-50-HI) relative to the parental HEC-50 cells. We further identified miR-124 as a direct regulator of IQGAP1 in EC cells. Enforced expression of miR-124 suppresses EC cell invasion and proliferation. The expression of IQGAP1 mRNA was significantly elevated in EC tissues, while the expression of miR-124 was decreased. The downregulation of miR-124 correlates with a poor survival outcome for patients with EC. Treating EC cells with the demethylating agent 5-aza-2'-deoxycytidine increased miR-124 expression and down-regulated IQGAP1 levels. Our data suggest that IQGAP1 promotes EMT, migration and invasion of EC cells. MiR-124, a novel tumor suppressor miRNA that is epigenetically silenced in EC, can reverse EMT and the invasive properties, by attenuating the expression of the IQGAP1 oncogene.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 3.0 Unported
PISSN	1949-2553
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.18632/oncotarget.7754