The miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth in epithelial tumor cell lines

被引:12
|
作者
Kobayashi, Kazuyoshi [1 ]
Sakurai, Kouhei [1 ]
Hiramatsu, Hiroaki [1 ]
Inada, Ken-ichi [3 ]
Shiogama, Kazuya [3 ]
Nakamura, Shinya [1 ]
Suemasa, Fumiko [1 ]
Kobayashi, Kyosuke [1 ]
Imoto, Seiya [2 ]
Haraguchi, Takeshi [1 ]
Ito, Hiroaki [1 ]
Ishizaka, Aya [1 ]
Tsutsumi, Yutaka [3 ]
Iba, Hideo [1 ]
机构
[1] Univ Tokyo, Dept Microbiol & Immunol, Div Host Parasite Interact, Tokyo, Japan
[2] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Lab DNA Informat Anal, Tokyo, Japan
[3] Fujita Hlth Univ, Fac Med, Dept Pathol 1, Toyoake, Aichi, Japan
来源
SCIENTIFIC REPORTS | 2015年 / 5卷
关键词
SWI/SNF COMPLEX; GENE-EXPRESSION; UP-REGULATION; C-MET; MESENCHYMAL TRANSITION; TRANSCRIPTION FACTOR; PLASMA-MEMBRANE; CANCER-CELLS; LUNG-CANCER; BRM;
D O I
10.1038/srep08428
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In epithelial cells, miRNA-199a-5p/-3p and Brm, a catalytic subunit of the SWI/SNF complex were previously shown to form a double-negative feedback loop through EGR1, by which human cancer cell lines tend to fall into either of the steady states, types 1 [miR-199a(2)/Brm(1)/EGR1(2)] and 2 [miR-199a(1)/Brm (2)/EGR1(1)]. We show here, that type 2 cells, unlike type 1, failed to form colonies in soft agar, and that CD44, MET, CAV1 and CAV2 (miR-199a targets), all of which function as plasma membrane sensors and can co-localize in caveolae, are expressed specifically in type 1 cells. Single knockdown of any of them suppressed anchorage-independent growth of type 1 cells, indicating that the miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth. Importantly, two coherent feedforward loops are integrated into this axis, supporting the robustness of type 1-specific gene expression and exemplifying how the miRNA-target gene relationship can be stably sustained in a variety of epithelial tumors.
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页数:11
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