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MicroRNA-885-3p inhibits the growth of HT-29 colon cancer cell xenografts by disrupting angiogenesis via targeting BMPR1A and blocking BMP/Smad/Id1 signaling

Oncogene volume 34, pages 1968–1978 (2015)Cite this article

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Abstract

The previous studies in this lab discovered that microRNA-885-3p (miR-885-3p) was regulated by a sulfated polysaccharide that bound to bone morphogenetic protein receptor, type IA (BMPR1A) to inhibit angiogenesis. However, its specific role and its mechanism of action in tumor cells have not been elucidated. We show that miR-885-3p markedly suppresses angiogenesis in vitro and in vivo. MiR-885-3p inhibits Smad1/5/8 phosphorylation and downregulates DNA-binding protein inhibitor ID-1 (Id1), a proangiogenic factor, by targeting BMPR1A, leading to impaired angiogenesis. Overexpression or silencing of BMPR1A affects angiogenesis in a Smad/Id1-dependent manner. We further show that miR-885-3p impairs the growth of HT-29 colon cancer cell xenografts in nude mice by suppressing angiogenesis through disruption of BMPR1A and Smad/Id1 signaling. These results support a novel role for miR-885-3p in tumor angiogenesis by targeting BMPR1A, which regulates a proangiogenic factor, and provide new evidence that targeting miRNAs might be an effective therapeutic strategy for improving colon cancer treatment.

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References

  1. Martello G, Rosato A, Ferrari F, Manfrin A, Cordenonsi M, Dupont S et al. A microrna targeting dicer for metastasis control. Cell 2010; 141: 1195–1207.

    Article  CAS  PubMed  Google Scholar 

  2. Lai EC . Micro RNAs are complementary to 3' UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet 2002; 30: 363–364.

    Article  CAS  PubMed  Google Scholar 

  3. le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A et al. Regulation of the p27(kip1) tumor suppressor by mir-221 and mir-222 promotes cancer cell proliferation. EMBO J 2007; 26: 3699–3708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Suarez Y, Sessa WC . Micrornas as novel regulators of angiogenesis. Circ Res 2009; 104: 442–454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Folkman J, Shing Y . Angiogenesis. J Biol Chem 1992; 267: 10931–10934.

    CAS  PubMed  Google Scholar 

  6. Folkman J . Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285: 1182–1186.

    Article  CAS  PubMed  Google Scholar 

  7. Perk J, Gil-Bazo I, Chin Y, de Candia P, Chen JJ, Zhao Y et al. Reassessment of id1 protein expression in human mammary, prostate, and bladder cancers using a monospecific rabbit monoclonal anti-id1 antibody. Cancer Res 2006; 66: 10870–10877.

    Article  CAS  PubMed  Google Scholar 

  8. Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O'Reilly R et al. Id1 and id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 1999; 401: 670–677.

    Article  CAS  PubMed  Google Scholar 

  9. Qiu H, Yang B, Pei ZC, Zhang Z, Ding K . Wss25 inhibits growth of xenografted hepatocellular cancer cells in nude mice by disrupting angiogenesis via blocking bone morphogenetic protein (bmp)/smad/id1 signaling. J Biol Chem 2010; 285: 32638–32646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Miyazono K, Miyazawa K . Id: A target of bmp signaling. Sci STKE 2002; 2002: pe40.

    PubMed  Google Scholar 

  11. Okamoto K, Ishiguro T, Midorikawa Y, Ohata H, Izumiya M, Tsuchiya N et al. Mir-493 induction during carcinogenesis blocks metastatic settlement of colon cancer cells in liver. EMBO J 2012; 31: 1752–1763.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ventura A, Jacks T . Micrornas and cancer: short RNAs go a long way. Cell 2009; 136: 586–591.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Dong Y, Wu WK, Wu CW, Sung JJ, Yu J, Ng SS et al. Microrna dysregulation in colorectal cancer: a clinical perspective. Br J Cancer 2011; 104: 893–898.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wu WK, Law PT, Lee CW, Cho CH, Fan D, Wu K et al. Microrna in colorectal cancer: from benchtop to bedside. Carcinogenesis 2011; 32: 247–253.

    Article  CAS  PubMed  Google Scholar 

  15. Valdimarsdottir G, Goumans MJ, Rosendahl A, Brugman M, Itoh S, Lebrin F et al. Stimulation of id1 expression by bone morphogenetic protein is sufficient and necessary for bone morphogenetic protein-induced activation of endothelial cells. Circulation 2002; 106: 2263–2270.

    Article  CAS  PubMed  Google Scholar 

  16. Kerbel RS . Tumor angiogenesis. N Engl J Med 2008; 358: 2039–2049.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yamakuchi M, Lotterman CD, Bao C, Hruban RH, Karim B, Mendell JT et al. P53-induced microrna-107 inhibits hif-1 and tumor angiogenesis. Proc Natl Acad Sci USA 2010; 107: 6334–6339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cha ST, Chen PS, Johansson G, Chu CY, Wang MY, Jeng YM et al. Microrna-519c suppresses hypoxia-inducible factor-1alpha expression and tumor angiogenesis. Cancer Res 2010; 70: 2675–2685.

    Article  CAS  PubMed  Google Scholar 

  19. Guled M, Lahti L, Lindholm PM, Salmenkivi K, Bagwan I, Nicholson AG et al. Cdkn2a, nf2, and jun are dysregulated among other genes by mirnas in malignant mesothelioma—a miRNA microarray analysis. Gene Chromosomes Cancer 2009; 48: 615–623.

    Article  CAS  Google Scholar 

  20. Huang Y, Chuang AY, Ratovitski EA . Phospho-deltanp63alpha/mir-885-3p axis in tumor cell life and cell death upon cisplatin exposure. Cell Cycle 2011; 10: 3938–3947.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mishina Y, Starbuck MW, Gentile MA, Fukuda T, Kasparcova V, Seedor JG et al. Bone morphogenetic protein type ia receptor signaling regulates postnatal osteoblast function and bone remodeling. J Biol Chem 2004; 279: 27560–27566.

    Article  CAS  PubMed  Google Scholar 

  22. El-Bizri N, Wang L, Merklinger SL, Guignabert C, Desai T, Urashima T et al. Smooth muscle protein 22alpha-mediated patchy deletion of bmpr1a impairs cardiac contractility but protects against pulmonary vascular remodeling. Circ Res 2008; 102: 380–388.

    Article  CAS  PubMed  Google Scholar 

  23. Goulley J, Dahl U, Baeza N, Mishina Y, Edlund H . Bmp4-bmpr1a signaling in beta cells is required for and augments glucose-stimulated insulin secretion. Cell Metab 2007; 5: 207–219.

    Article  CAS  PubMed  Google Scholar 

  24. Zhou XP, Woodford-Richens K, Lehtonen R, Kurose K, Aldred M, Hampel H et al. Germline mutations in bmpr1a/alk3 cause a subset of cases of juvenile polyposis syndrome and of cowden and Bannayan–Riley–Ruvalcaba syndromes. Am J Hum Genet 2001; 69: 704–711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. van Hattem WA, Brosens LA, de Leng WW, Morsink FH, Lens S, Carvalho R et al. Large genomic deletions of smad4, bmpr1a and pten in juvenile polyposis. Gut 2008; 57: 623–627.

    Article  CAS  PubMed  Google Scholar 

  26. Xiao F, Qiu H, Zhou L, Shen X, Yang L, Ding K et al. Wss25 inhibits dicer, downregulating microrna-210, which targets ephrin-a3, to suppress human microvascular endothelial cell (hmec-1) tube formation. Glycobiology 2013; 23: 524–535.

    Article  CAS  PubMed  Google Scholar 

  27. Rubinson DA, Dillon CP, Kwiatkowski AV, Sievers C, Yang L, Kopinja J et al. A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat Genet 2003; 33: 401–406.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (81171914, 31230022), the New Drug Creation and Manufacturing Program (2012ZX09301001-003) and the National Science Fund for Distinguished Young Scholars in China (81125025).

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Authors and Affiliations

  1. Glycochemistry and Glycobiology Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

    F Xiao, H Qiu, H Cui, X Ni, J Li, W Liao, L Lu & K Ding

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  1. F Xiao
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  2. H Qiu
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  3. H Cui
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  4. X Ni
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Correspondence to K Ding.

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Xiao, F., Qiu, H., Cui, H. et al. MicroRNA-885-3p inhibits the growth of HT-29 colon cancer cell xenografts by disrupting angiogenesis via targeting BMPR1A and blocking BMP/Smad/Id1 signaling. Oncogene 34, 1968–1978 (2015). https://doi.org/10.1038/onc.2014.134

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