MicroRNA-140 mediates RB tumor suppressor function to control stem cell-like activity through interleukin-6

フォーマット:

論文

責任表示:

Yoshida, Akiyo ; Kitajima, Shunsuke ; Li, Fengkai ; Cheng, Chaoyang ; Takegami, Yujiro ; Kohno, Susumu ; Wan, Yuan Song ; Hayashi, Naoyuki ; Muranaka, Hayato ; Nishimoto, Yuuki ; Nagatani, Naoko ; Nishiuchi, Takumi ; Thai, Tran C ; Suzuki, Sawako ; Nakao, Shinji ; Tanaka, Tomoaki ; Hirose, Osamu ; Barbie, David A. ; Takahashi, Chiaki

言語:

英語

出版情報:

Impact Journals LLC, 2017-01-01

著者名:

Yoshida, Akiyo

Kitajima, Shunsuke

Li, Fengkai

Cheng, Chaoyang

Takegami, Yujiro

Kohno, Susumu

Wan, Yuan Song

Hayashi, Naoyuki

Muranaka, Hayato

Nishimoto, Yuuki

Nagatani, Naoko

Nishiuchi, Takumi

Thai, Tran C

Suzuki, Sawako

Nakao, Shinji

Tanaka, Tomoaki

Hirose, Osamu

Barbie, David A.

Takahashi, Chiaki

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掲載情報:

Oncotarget

ISSN:

1949-2553      

巻:

8

通号:

8

開始ページ:

13872

終了ページ:

13885

バージョン:

publisher

概要:

We established an in vitro cell culture system to determine novel activities of the retinoblastoma (Rb) protein during tumor progression. Rb depletion in p53-null mouse-derived soft tissue sarcoma cells induced a spherogenic phenotype. Cells retrieved from Rb-depleted spheres exhibited slower proliferation and less efficient BrdU incorporation, however, much higher spherogenic activity and aggressive behavior. We discovered six miRNAs, … including mmu-miR-18a, -25, -29b, -140, -337, and -1839, whose expression levels correlated tightly with the Rb status and spherogenic activity. Among these, mmu-miR-140 appeared to be positively controlled by Rb and to antagonize the effect of Rb depletion on spherogenesis and tumorigenesis. Furthermore, among genes potentially targeted by mmu-miR-140, Il-6 was upregulated by Rb depletion and downregulated by mmu-mir-140 overexpression. Altogether, we demonstrate the possibility that mmu-mir-140 mediates the Rb function to downregulate Il-6 by targeting its 3'-untranslated region. Finally, we detected the same relationship among RB, hsa-miR-140 and IL-6 in a human breast cancer cell line MCF-7. Because IL-6 is a critical modulator of malignant features of cancer cells and the RB pathway is impaired in the majority of cancers, hsa-miR-140 might be a promising therapeutic tool that disrupts linkage between tumor suppressor inactivation and pro-inflammatory cytokine response.<br />Supplementary Table1 and Supplementary Table2: We offer the table data with an Excel file 続きを見る

URL:

http://hdl.handle.net/2297/47088