Tumor Biology

, Volume 37, Issue 8, pp 10763–10773 | Cite as

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

  • Rui Yi
  • Yao Li
  • Feiliang Wang
  • Jianguo Gu
  • Tomoya Isaji
  • Jian Li
  • Ruomei Qi
  • Xiaoquan Zhu
  • Yanyang Zhao
Original Article

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.

Keywords

miR-130b TGF-β1 Cell motility Integrin 

Notes

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 Beijing Natural Science Foundation 5102039.

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

13277_2016_4965_Fig6_ESM.jpg (530 kb)
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)

13277_2016_4965_Fig7_ESM.jpg (1.1 mb)
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)

13277_2016_4965_MOESM1_ESM.xlsx (43 kb)
Supplementary Table 1 The clinicopathologic features of 39 patients. (XLSX 42 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Rui Yi
    • 1
    • 2
  • Yao Li
    • 3
  • Feiliang Wang
    • 2
    • 3
  • Jianguo Gu
    • 4
  • Tomoya Isaji
    • 4
  • Jian Li
    • 2
  • Ruomei Qi
    • 2
  • Xiaoquan Zhu
    • 2
  • Yanyang Zhao
    • 1
    • 2
  1. 1.Peking University Fifth School of Clinical MedicineBeijing HospitalBeijingChina
  2. 2.The Key Laboratory of GeriatricsBeijing Hospital and Beijing Institute of Geriatrics, Ministry of HealthBeijingChina
  3. 3.Department of SurgeryBeijing HospitalBeijingChina
  4. 4.Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and GlycobiologyTohoku Pharmaceutical UniversitySendaiJapan

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