The miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth in epithelial tumor cell lines
Copyright policy )The miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth in epithelial tumor cell lines
AbstractIn 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.
- Fujita Health University Japan
- University of Tokyo Japan
Caveolin 2, Gene Expression Profiling, Carcinoma, Caveolin 1, Proto-Oncogene Proteins c-met, Models, Biological, Article, Gene Expression Regulation, Neoplastic, MicroRNAs, Hyaluronan Receptors, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Gene Knockdown Techniques, Humans, Early Growth Response Protein 1, Transcription Factors
Caveolin 2, Gene Expression Profiling, Carcinoma, Caveolin 1, Proto-Oncogene Proteins c-met, Models, Biological, Article, Gene Expression Regulation, Neoplastic, MicroRNAs, Hyaluronan Receptors, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Gene Knockdown Techniques, Humans, Early Growth Response Protein 1, Transcription Factors
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