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

Kazuyoshi Kobayashi, Kouhei Sakurai, Hiroaki Hiramatsu, Ken Ichi Inada, Kazuya Shiogama, Shinya Nakamura, Fumiko Suemasa, Kyosuke Kobayashi, Seiya Imoto, Takeshi Haraguchi, Hiroaki Ito, Aya Ishizaka, Yutaka Tsutsumi, Hideo Iba

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Abstract

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.

Original languageEnglish
Article number8428
Pages (from-to)8428
Number of pages1
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 02-2015

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    Kobayashi, K., Sakurai, K., Hiramatsu, H., Inada, K. I., Shiogama, K., Nakamura, S., Suemasa, F., Kobayashi, K., Imoto, S., Haraguchi, T., Ito, H., Ishizaka, A., Tsutsumi, Y., & Iba, H. (2015). The miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth in epithelial tumor cell lines. Scientific reports, 5, 8428. [8428]. https://doi.org/10.1038/srep08428