GSBS Student Publications


miR-21 and miR-31 Converge on TIAM1 to Regulate Migration and Invasion of Colon Carcinoma Cells

Student Author(s)

Charisa Cottonham

GSBS Program

Interdisciplinary Graduate Program

UMMS Affiliation

Program in Molecular Medicine



Document Type


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


Related Resources

Link to article in PubMed

Journal Title

The Journal of Biological Chemistry

PubMed ID