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Transforming growth factor (TGF) β1 acted through miR-130b to increase integrin α5 to promote migration of colorectal cancer cells

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Tumor Biology

Abstract

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.

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Acknowledgments

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 Bei**g Natural Science Foundation 5102039.

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Authors and Affiliations

  1. Peking University Fifth School of Clinical Medicine, Bei**g Hospital, Bei**g, 100730, China

    Rui Yi & Yanyang Zhao

  2. The Key Laboratory of Geriatrics, Bei**g Hospital and Bei**g Institute of Geriatrics, Ministry of Health, Bei**g, 100730, China

    Rui Yi, Feiliang Wang, Jian Li, Ruomei Qi, **aoquan Zhu & Yanyang Zhao

  3. Department of Surgery, Bei**g Hospital, Bei**g, 100730, China

    Yao Li & Feiliang Wang

  4. Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, Japan

    Jianguo Gu & Tomoya Isaji

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  1. Rui Yi
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Correspondence to **aoquan Zhu or Yanyang Zhao.

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Supplementary Figure 1

Transwell migration assays of SW480 cells treated without or with 20 ng/mL TGF-β1 for 24 hours (scale bar=100 μm; mean±s.d.; n=3; *, P <0.05). Representative images of migrated cells were shown. (JPG 529 kb)

Supplementary Figure 2

The putative binding sites with the seed region of miR-130b were at 187-193bp (underlined) and 902-908bp (underlined) of the full-length integrin α5 3′UTR. (JPG 1117 kb)

Supplementary Table 1

The clinicopathologic features of 39 patients. (XLSX 42 kb)

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Yi, R., Li, Y., Wang, F. et al. Transforming growth factor (TGF) β1 acted through miR-130b to increase integrin α5 to promote migration of colorectal cancer cells. Tumor Biol. 37, 10763–10773 (2016). https://doi.org/10.1007/s13277-016-4965-6

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  • DOI: https://doi.org/10.1007/s13277-016-4965-6

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