学術雑誌論文 MicroRNA-140 mediates RB tumor suppressor function to control stem cell-like activity through interleukin-6

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

8 ( 8 )  , pp.13872 - 13885 , 2017-01-01 , Impact Journals LLC
ISSN:1949-2553
内容記述
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.
Supplementary Table1 and Supplementary Table2: We offer the table data with an Excel file
本文を読む

https://kanazawa-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27516&item_no=1&attribute_id=26&file_no=1

https://kanazawa-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27516&item_no=1&attribute_id=26&file_no=2

https://kanazawa-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27516&item_no=1&attribute_id=26&file_no=3

https://kanazawa-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27516&item_no=1&attribute_id=26&file_no=4

このアイテムのアクセス数:  回

その他の情報