miR-21 and miR-31 converge on TIAM1 to regulate migration and invasion of colon carcinoma cells.
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.
Cottonham
Charisa L
CL
University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Kaneko
Satoshi
S
Xu
Lan
L
D015152:Blotting, Northern; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D020662:Guanine Nucleotide Exchange Factors; C524940:MIRN21 microRNA, human; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha
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