The miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth in epithelial tumor cell lines.
The miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth in epithelial tumor cell lines.
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DOI：
10.1038/srep08428
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发表时间：
2015-02-12
影响因子：
4.6
通讯作者：
Iba H
中科院分区：
文献类型：
--
作者：
Kobayashi K;Sakurai K;Hiramatsu H;Inada K;Shiogama K;Nakamura S;Suemasa F;Kobayashi K;Imoto S;Haraguchi T;Ito H;Ishizaka A;Tsutsumi Y;Iba H
在上皮细胞中，miRNA-199a-5p/-3p和Brm（SWI/SNF复合物的催化亚基）先前被证明可通过EGR1形成双负反馈环，通过该环，人类癌细胞系往往会陷入稳态，即1型[miR-199a(−)/Brm(+)/EGR1(−)]和2型[miR-199a(+)/Brm] (-)/EGR1(+)]。我们在此表明，与 1 型细胞不同，2 型细胞无法在软琼脂中形成集落，而 CD44、MET、CAV1 和 CAV2（miR-199a 靶标）均作为质膜传感器发挥作用，并且可以在小凹中共定位，在 1 型细胞中特异性表达。其中任何一个的单一敲低都会抑制 1 型细胞的贴壁依赖性生长，表明 miR-199a/Brm/EGR1 轴是贴壁依赖性生长的决定因素。重要的是，两个连贯的前馈环被集成到该轴中，支持 1 型特异性基因表达的稳健性，并举例说明了 miRNA-靶基因关系如何在各种上皮肿瘤中稳定维持。
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(−)/Brm(+)/EGR1(−)] and 2 [miR-199a(+)/Brm (−)/EGR1(+)]. 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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影响因子：
11.2
作者：
Hartman ZC;Poage GM;den Hollander P;Tsimelzon A;Hill J;Panupinthu N;Zhang Y;Mazumdar A;Hilsenbeck SG;Mills GB;Brown PH
通讯作者：
Brown PH
影响因子：
3.9
作者：
Mariniello, Barbara;Rosato, Antonio;Mantero, Franco
通讯作者：
Mantero, Franco
DOI：
10.1016/j.bbamcr.2013.05.003
发表时间：
2013-10-01
影响因子：
5.1
作者：
Kwon, Hayeong;Lee, Jaewoong;Pak, Yunbae
通讯作者：
Pak, Yunbae
影响因子：
5.6
作者：
Gurtan, Allan M.;Sharp, Phillip A.
通讯作者：
Sharp, Phillip A.
影响因子：
8
作者：
Bilsland, AE;Anderson, CJ;Keith, WN
通讯作者：
Keith, WN