TY - JOUR
T1 - The miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth in epithelial tumor cell lines
AU - Kobayashi, Kazuyoshi
AU - Sakurai, Kohei
AU - Hiramatsu, Hiroaki
AU - Inada, Ken Ichi
AU - Shiogama, Kazuya
AU - Nakamura, Shinya
AU - Suemasa, Fumiko
AU - Kobayashi, Kyosuke
AU - Imoto, Seiya
AU - Haraguchi, Takeshi
AU - Ito, Hiroaki
AU - Ishizaka, Aya
AU - Tsutsumi, Yutaka
AU - Iba, Hideo
N1 - Funding Information:
We thank S. Kawaura and A. Kato for their assistance in preparing the manuscript. This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas (22300318) and on Innovative Areas (24115007) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan.
PY - 2015/2
Y1 - 2015/2
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84923165673
UR - https://www.scopus.com/pages/publications/84923165673#tab=citedBy
U2 - 10.1038/srep08428
DO - 10.1038/srep08428
M3 - Article
C2 - 25673149
AN - SCOPUS:84923165673
SN - 2045-2322
VL - 5
SP - 8428
JO - Scientific reports
JF - Scientific reports
M1 - 8428
ER -
