Export file:


  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text


  • Citation Only
  • Citation and Abstract

MicroRNA-527 inhibits TGF-β/SMAD induced epithelial-mesenchymal transition via downregulating SULF2 expression in non-small-cell lung cancer

Department of Medical Oncology, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian 116033, China.

Special Issues: Advanced Big Data Analysis for Precision Medicine

Objective: To explore the potential mechanism which miR-527 targeting the heparan sulfate 6-O-endosulfatase (SULF2) regulates TGF-β/SMAD signaling pathway induced epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC). Methods: 38 pairs of lung tumor biopsies and corresponding paracancerous biopsies were obtained from NSCLC patients with surgical resection, normal human bronchial epithelial BEAS-2B cells and five NSCLS cell lines were applied for our study. miR-527 and SULF2 expression were determined by qRT-PCR and immunohistochemistry. MiR-527 and SULF2 biological link were predicted by Targetscan.org and tested by dual luciferase. Cells proliferation and apoptosis were respectively detected by EDU staining and flow cytometry. Cells migration was examined by transwell and scratch-wound assay. Expression of proteins related to EMT and TGF-β/SMAD signaling pathway, such as E-cadherin, N-cadherin, p-Samd3 and p-Smad2, was detected by western blot. Results: miR-527 expression was decreased in lung tumor tissues and NSCLS cell lines, conversely, SULF2 expression was significantly increased. In addition, we found that miR-527 targeted 3’-untranslated regions (3’-UTR) of SULF2 and mediated its expression. Overexpression of miR-527 evidently suppressed NSCLC proliferation, invasion and EMT via TGF-β/SMAD signaling pathway. Moreover, the silence of SULF2 exhibited a similar effect. Conclusion: miR-527 targeting SULF2 down-regulated SULF2 expression, concurrently, suppressed NSCLC epithelial-mesenchymal transition and invasion via inhibiting TGF-β/SMAD signaling pathway.
  Article Metrics

Keywords miR-527; SULF2; TGF-β/SMAD signaling pathway; NSCLC; EMT

Citation: Wei Huo, Xiao-Min Zhu, Xin-Yan Pan, Min Du, Zhuo Sun, Zhi-Min Li. MicroRNA-527 inhibits TGF-β/SMAD induced epithelial-mesenchymal transition via downregulating SULF2 expression in non-small-cell lung cancer. Mathematical Biosciences and Engineering, 2019, 16(5): 4607-4621. doi: 10.3934/mbe.2019231


  • 1. J. Su, J. Liao, L. Gao, et al., Analysis of small nucleolar RNAs in sputum for lung cancer diagnosis, Oncotarget, 7 (2016), 5131–5142.
  • 2. L. A. Torre, R. L. Siegel and A. Jemal, Lung cancer statistics, Adv. Exp. Med. Biol., 893 (2016), 1–19.
  • 3. L. K. Hou, Y. S. Ma, Y. Han, et al., Association of microRNA-33a molecular signature with non-small cell lung cancer diagnosis and prognosis after chemotherapy, PLoS One, 12 (2017), e0170431.
  • 4. B. C. Roy, T. Kohno, R. Iwakawa, et al., Involvement of LKB1 in epithelial-mesenchymal transition (EMT) of human lung cancer cells, Lung Cancer, 70 (2010), 136–145.
  • 5. B. Salehi, E. M. Varoni, M. Sharifi-Rad, et al., Epithelial-mesenchymal transition as a target for botanicals in cancer metastasis, Phytomedicine, 55 (2019), 125–136.
  • 6. Y. Ke, W. Zhao, J. Xiong, et al., miR-149 inhibits non-small-cell lung cancer cells emt by targeting FOXM1, Biochem. Res. Int., 2013 (2013), 506731.
  • 7. P. Nasarre, R. M. Gemmill, V. A. Potiron, et al., Neuropilin-2 Is upregulated in lung cancer cells during TGF-β1-induced epithelial-mesenchymal transition, Cancer Res., 73 (2013), 7111–7121.
  • 8. L. Wang, X. Tong, Z. Zhou, et al., Circular RNA hsa_circ_0008305 (circPTK2) inhibits TGF-β-induced epithelial-mesenchymal transition and metastasis by controlling TIF1gamma in non-small cell lung cancer, Mol. Cancer, 17 (2018), 140.
  • 9. Y. Xiang, Y. Zhang, Y. Tang, et al., MALAT1 modulates TGF-β1-induced endothelial-to-mesenchymal transition through downregulation of miR-145, Cell Physiol. Biochem., 42 (2017), 357–372.
  • 10. L. Fang, S. Wu, X. Zhu, et al., MYEOV functions as an amplified competing endogenous RNA in promoting metastasis by activating TGF-β pathway in NSCLC, Oncogene, 38 (2019), 896–912.
  • 11. M. Tessema, C. M. Yingling, C. L. Thomas, et al., SULF2 methylation is prognostic for lung cancer survival and increases sensitivity to topoisomerase-I inhibitors via induction of ISG15, Oncogene, 31 (2012), 4107–4116.
  • 12. G. Chen, I. Nakamura, R. Dhanasekaran, et al., Transcriptional induction of periostin by a sulfatase 2-tgf-β1-smad signaling axis mediates tumor angiogenesis in hepatocellular carcinoma, Cancer Res., 77 (2017), 632–645.
  • 13. M. Tantawy, M. G. Elzayat, D. Yehia, et al., Identification of microRNA signature in different pediatric brain tumors, Genet. Mol. Biol., 41 (2018), 27–34.
  • 14. 14. L. Rodriguez Calleja, C. Jacques, F. Lamoureux, et al., ΔNp63α silences a miRNA program to aberrantly initiate a wound-healing program that promotes TGF-β-induced metastasis, Cancer Res., 76 (2016), 3236–3251.
  • 15. A. P. Mishra, B. Salehi, M. Sharifi-Rad, et al., Programmed cell death, from a cancer perspective: An overview, Mol. Diagn. Ther., 22 (2018), 281–295.
  • 16. B. Salehi, P. Zucca, M. Sharifi-Rad, et al., Phytotherapeutics in cancer invasion and metastasis, Phytother Res., 32 (2018), 1425–1449.
  • 17. C. Lu, H. Wang, S. Chen, et al., Baicalein inhibits cell growth and increases cisplatin sensitivity of A549 and H460 cells via miR-424-3p and targeting PTEN/PI3K/Akt pathway, J. Cell Mol. Med., 22 (2018), 2478–2487.
  • 18. M. Zhang, C. Gao, Y. Yang, et al., MiR-424 Promotes non-small cell lung cancer progression and metastasis through regulating the tumor suppressor gene TNFAIP1, Cell Physiol. Biochem., 42 (2017), 211–221.
  • 19. A. Izzotti, G. A. Calin, P. Arrigo, et al., Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke, Faseb J., 23 (2009), 806–812.
  • 20. Z. Zhou, X. Niu, C. Li, et al., Inhibition of the growth of non-small cell lung cancer by miRNA-1271, Am. J. Transl. Res., 7 (2015), 1917–1924.
  • 21. X. C. Wang, L. Q. Du, L. L. Tian, et al., Expression and function of miRNA in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer, Lung Cancer, 72 (2011), 92–99.
  • 22. F. K. Johansson, H. Goransson and B. Westermark, Expression analysis of genes involved in brain tumor progression driven by retroviral insertional mutagenesis in mice, Oncogene, 24 (2005), 3896–3905.
  • 23. M. Morimoto-Tomita, K. Uchimura, A. Bistrup, et al., Sulf-2, a proangiogenic heparan sulfate endosulfatase, is upregulated in breast cancer, Neoplasia, 7 (2005), 1001–1010.
  • 24. K. Uchimura, M. Morimoto-Tomita, A. Bistrup, et al., HSulf-2, an extracellular endoglucosamine-6-sulfatase, selectively mobilizes heparin-bound growth factors and chemokines: effects on VEGF, FGF-1, and SDF-1, BMC Biochem., 7 (2006), 2.
  • 25. J. P. Lai, D. S. Sandhu, C. Yu, et al., Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma, Hepatology, 47 (2008), 1211–1222.
  • 26. H. Lemjabbar-Alaoui, A. van Zante, M. S. Singer, et al., Sulf-2, a heparan sulfate endosulfatase, promotes human lung carcinogenesis, Oncogene, 29 (2010), 635–646.
  • 27. J. P. Thiery, H. Acloque, R. Y. Huang, et al., Epithelial-mesenchymal transitions in development and disease, Cell, 139 (2009), 871–890.
  • 28. J. Yang and R. A. Weinberg, Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis, Dev. Cell, 14 (2008), 818–829.
  • 29. J. P. Thiery, Epithelial-mesenchymal transitions in tumour progression, Nat. Rev. Cancer., 2 (2002), 442–454.
  • 30. J. Lim and J. P. Thiery, Epithelial-mesenchymal transitions: Insights from development, Development, 139 (2012), 3471–3486.
  • 31. D. Hanahan and R. A. Weinberg, Hallmarks of cancer: The next generation, Cell, 144 (2011), 646–674.
  • 32. S. Lamouille, J. Xu and R. Derynck, Molecular mechanisms of epithelial-mesenchymal transition, Nat. Rev. Mol. Cell Biol., 15 (2014), 178–196.


This article has been cited by

  • 1. Qingjie Xian, Ronglei Zhao, Juanjuan Fu, MicroRNA-527 Induces Proliferation and Cell Cycle in Esophageal Squamous Cell Carcinoma Cells by Repressing PH Domain Leucine-Rich-Repeats Protein Phosphatase 2, Dose-Response, 2020, 18, 2, 155932582092868, 10.1177/1559325820928687

Reader Comments

your name: *   your email: *  

© 2019 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Export Citation

Copyright © AIMS Press All Rights Reserved