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

Kazuyoshi Kobayashi, Kohei 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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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
Number of pages1
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 01-01-2015

Fingerprint

Tumor Cell Line
Epithelial Cells
MicroRNAs
Growth
Caveolae
Agar
Catalytic Domain
Neoplasms
Cell Membrane
Gene Expression
Cell Line
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Kobayashi, Kazuyoshi ; Sakurai, Kohei ; Hiramatsu, Hiroaki ; Inada, Ken Ichi ; Shiogama, Kazuya ; Nakamura, Shinya ; Suemasa, Fumiko ; Kobayashi, Kyosuke ; Imoto, Seiya ; Haraguchi, Takeshi ; Ito, Hiroaki ; Ishizaka, Aya ; Tsutsumi, Yutaka ; Iba, Hideo. / The miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth in epithelial tumor cell lines. In: Scientific Reports. 2015 ; Vol. 5.
@article{a885bcfc558d4d5a8e961b1199a87b13,
title = "The miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth in epithelial tumor cell lines",
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.",
author = "Kazuyoshi Kobayashi and Kohei Sakurai and Hiroaki Hiramatsu and Inada, {Ken Ichi} and Kazuya Shiogama and Shinya Nakamura and Fumiko Suemasa and Kyosuke Kobayashi and Seiya Imoto and Takeshi Haraguchi and Hiroaki Ito and Aya Ishizaka and Yutaka Tsutsumi and Hideo Iba",
year = "2015",
month = "1",
day = "1",
doi = "10.1038/srep08428",
language = "English",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

Kobayashi, K, Sakurai, K, Hiramatsu, H, Inada, KI, 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, vol. 5. https://doi.org/10.1038/srep08428

The miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth in epithelial tumor cell lines. / Kobayashi, Kazuyoshi; Sakurai, Kohei; Hiramatsu, Hiroaki; Inada, Ken Ichi; Shiogama, Kazuya; Nakamura, Shinya; Suemasa, Fumiko; Kobayashi, Kyosuke; Imoto, Seiya; Haraguchi, Takeshi; Ito, Hiroaki; Ishizaka, Aya; Tsutsumi, Yutaka; Iba, Hideo.

In: Scientific Reports, Vol. 5, 01.01.2015.

Research output: Contribution to journalArticle

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

PY - 2015/1/1

Y1 - 2015/1/1

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 - http://www.scopus.com/inward/record.url?scp=84923165673&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923165673&partnerID=8YFLogxK

U2 - 10.1038/srep08428

DO - 10.1038/srep08428

M3 - Article

C2 - 25673149

AN - SCOPUS:84923165673

VL - 5

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

ER -