miR-21 and miR-31 Converge on TIAM1 to Regulate Migration and Invasion of Colon Carcinoma Cells
Interdisciplinary Graduate Program
Program in Molecular Medicine
Medical Subject Headings
Blotting, Northern; Cell Adhesion; Cell Line; Cell Line, Tumor; Cell Movement; Colonic Neoplasms; Epithelial-Mesenchymal Transition; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Guanine Nucleotide Exchange Factors; HEK293 Cells; Humans; MicroRNAs; Neoplasm Invasiveness; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha
Biochemistry, Biophysics, and Structural Biology | Life Sciences | Medicine and Health Sciences
TGF-β promotes cell migration and invasion, an attribute that is linked to the pro-metastasis function of this cytokine in late stage cancers. The LIM 1863 colon carcinoma organoid undergoes epithelial-mesenchymal transition (EMT) in response to TGF-β. This process is markedly accelerated by TNF-α, and we found that the levels of miR-21 and miR-31 were prominently elevated under the synergistic actions of TGF-β/TNF-α. Consistent with this, overexpression of either miR-21 or miR-31 significantly enhanced the effect of TGF-β alone on LIM 1863 morphological changes. More importantly, transwell assays demonstrated the positive effects of both miR-21 and miR-31 in TGF-β regulation of LIM 1863 motility and invasiveness. Elevated levels of miR-21 and miR-31 also enhanced motility and invasiveness of other colon carcinoma cell lines. We present compelling evidence that TIAM1, a guanidine exchange factor of the Rac GTPase, is a direct target of both miR-21 and miR-31. Indeed in LIM 1863 cells, suppression of TIAM1 is required for miR-21/miR-31 to enhance cell migration and invasion. Therefore, we have uncovered miR-21 and miR-31 as downstream effectors of TGF-β in facilitating invasion and metastasis of colon carcinoma cells.
Rights and Permissions
Citation: J Biol Chem. 2010 Nov 12;285(46):35293-302. Epub 2010 Sep 7. Link to article on publisher's website
DOI of Published Version
The Journal of Biological Chemistry
Cottonham, Charisa L.; Kaneko, Satoshi; and Xu, Lan, "miR-21 and miR-31 Converge on TIAM1 to Regulate Migration and Invasion of Colon Carcinoma Cells" (2010). GSBS Student Publications. 1683.