Transforming growth factor (TGF) β1 acted through miR-130b to increase integrin α5 to promote migration of colorectal cancer cells
Transforming growth factor (TGF)-β1 is a significant stimulator of tumor invasion and metastasis. More recently, it has been found that TGF-β1 acts through microRNAs to regulate their target genes to promote cancer progresses. However, such similar regulation is rarely reported in colorectal cancer (CRC). Here, we observed a decrease in TGF-β1 expression in CRC specimens, compared with matched adjacent normal tissues. In parallel, there was an increase in miR-130b characterized in the same samples by microarray assay. Further, treatment of CRC cells with TGF-β1 caused a significant decrease in the expression of miR-130b and an increased CRC cell migration. Luciferase reporter assay revealed that miR-130b directly targeted the 3′ untranslated region (3′UTR) region of integrin α5 gene, which encodes a key molecule involved in cell motility. Subsequently, in the overexpression of miR-130b CRC cells, we observed a decreased level of integrin α5 protein. The regulation of integrin α5 by miR-130b was further shown using the miR-130b mimics and inhibitor of miR-130b. And, knockdown miR-130b with inhibitor in the overexpression of miR-130b CRC cells recovered integrin α5 expression and integrin α5-mediated cell motility. Moreover, the inverse relevance between miR-130b and integrin α5 was also observed in CRC specimens. At last, the enhancement of integrin α5 in TGF-β1-treated cells can be reversed partly when rescuing miR-130b expression. Together, our findings suggested that TGF-β1 acted through miR-130b to promote integrin α5 expression, resulting in the enhanced migration of CRC cells.
KeywordsmiR-130b TGF-β1 Cell motility Integrin
This work was supported by National Natural Science Foundation of China Grant 81101859, National Natural Science Foundation of China Grant 81000780, National Natural Science Foundation of China Grant 81472408, National Natural Science Foundation of China Grant 81541152, and Beijing Natural Science Foundation 5102039.
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Conflicts of interest
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