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miR-335 suppresses migration and invasion by targeting ROCK1 in osteosarcoma cells

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Abstract

Accumulating evidence has shown that microRNAs are involved in multiple processes in cancer development and progression. Recently, miR-335 has been identified as a tumor-suppressing microRNA in many human cancers. However, the specific function of miR-335 in osteosarcoma is unclear at this point. In this study, we found that the expression of miR-335 in osteosarcoma tissues and cell lines was much lower than that in normal control, respectively, and the downregulated miR-335 was significantly associated with lymph-node metastasis. Transfection of miR-335 mimics could significantly inhibit the cell migration and invasion in MG-63 and U2OS osteosarcoma cell lines. Moreover, we also showed that ROCK1 was negatively regulated by miR-335 at the posttranscriptional level, via a specific target site within the 3′UTR by luciferase reporter assay. The expression of ROCK1 was inversely correlated with miR-335 expression in osteosarcoma tissues, and knockdown of ROCK1 by siRNA-inhibited osteosarcoma cells migration and invasion resembling that of miR-335 overexpression. Thus, our findings suggest that miR-335 acts as tumor suppressor by targeting the ROCK1 gene and inhibiting osteosarcoma cells migration and invasion. The findings of this study contribute to current understanding of the functions of miR-335 in osteosarcoma.

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References

  1. Mirabello L, Troisi RJ, Savage SA (2009) Osteosarcoma incidence and survival rates from 1973 to 2004: data from the surveillance, epidemiology, and end results program. Cancer 115:1531–1543

    Article  PubMed  Google Scholar 

  2. Marina N, Gebhardt M, Teot L, Gorlick R (2004) Biology and therapeutic advances for pediatric osteosarcoma. Oncologist 9:422–441

    Article  PubMed  Google Scholar 

  3. Wada T, Isu K, Takeda N, Usui M, Ishii S, Yamawaki S (1996) A preliminary report of neoadjuvant chemotherapy NSH-7 study in osteosarcoma: preoperative salvage chemotherapy based on clinical tumor response and the use of granulocyte colony-stimulating factor. Oncology 53:221–227

    Article  PubMed  CAS  Google Scholar 

  4. Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866

    Article  PubMed  CAS  Google Scholar 

  5. Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T (2007) Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 39:673–677

    Article  PubMed  CAS  Google Scholar 

  6. Shu M, Zhou Y, Zhu W, Zhang H, Wu S, Chen J, Yan G (2012) MicroRNA-335 is required for differentiation of malignant glioma cells induced by activation of cAMP/protein kinase A pathway. Mol Pharmacol 81:292–298

    Article  PubMed  CAS  Google Scholar 

  7. Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massagué J (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451:147–152

    Article  PubMed  CAS  Google Scholar 

  8. Wang F, Zheng Z, Guo J, Ding X (2010) Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol 119:586–593

    Article  PubMed  CAS  Google Scholar 

  9. Sorrentino A, Liu CG, Addario A, Peschle C, Scambia G, Ferlini C (2008) Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol Oncol 111:478–486

    Article  PubMed  CAS  Google Scholar 

  10. Xiong SW, Lin TX, Xu KW, Dong W, Ling XH, Jiang FN, Chen G, Zhong WD, Huang J (2013) MicroRNA-335 Acts as a Candidate Tumor Suppressor in Prostate Cancer. Pathol Oncol Res. doi:10.1007/s12253-013-9613-5

    Google Scholar 

  11. Yan Z, Xiong Y, Xu W, Gao J, Cheng Y, Wang Z, Chen F, Zheng G (2012) Identification of hsa-miR-335 as a prognostic signature in gastric cancer. PLoS One 7:e40037

    Article  PubMed  CAS  Google Scholar 

  12. Shu M, Zheng X, Wu S, Lu H, Leng T, Zhu W, Ou Y, Lin X, Lin Y, Xu D, Zhou Y, Yan G (2011) Targeting oncogenic miR-335 inhibits growth and invasion of malignant astrocytoma cells. Mol Cancer 10:59

    Article  PubMed  CAS  Google Scholar 

  13. Shi L, Jiang D, Sun G, Wan Y, Zhang S, Zeng Y, Pan T, Wang Z (2012) miR-335 promotes cell proliferation by directly targeting Rb1 in meningiomas. J Neurooncol 110:155–162

    Article  PubMed  CAS  Google Scholar 

  14. Xu Y, Zhao F, Wang Z, Song Y, Luo Y, Zhang X, Jiang L, Sun Z, Miao Z, Xu H (2012) MicroRNA-335 acts as a metastasis suppressor in gastric cancer by targeting Bcl-w and specificity protein 1. Oncogene 31:1398–1407

    Article  PubMed  CAS  Google Scholar 

  15. Zhang J, Ying ZZ, Tang ZL, Long LQ, Li K (2012) MicroRNA-148a promotes myogenic differentiation by targeting the ROCK1 gene. J Biol Chem 287:21093–210101

    Article  PubMed  CAS  Google Scholar 

  16. Cimino D, De Pittà C, Orso F, Zampini M, Casara S, Penna E, Quaglino E, Forni M, Damasco C, Pinatel E, Ponzone R, Romualdi C, Brisken C, De Bortoli M, Biglia N, Provero P, Lanfranchi G, Taverna D (2013) miR148b is a major coordinator of breast cancer progression in a relapse-associated microRNA signature by targeting ITGA5, ROCK1, PIK3CA, NRAS, and CSF1. FASEB J 27:1223–1235

    Article  PubMed  CAS  Google Scholar 

  17. Xu D, Takeshita F, Hino Y, Fukunaga S, Kudo Y, Tamaki A, Matsunaga J, Takahashi RU, Takata T, Shimamoto A, Ochiya T, Tahara H (2011) miR-22 represses cancer progression by inducing cellular senescence. J Cell Biol 93:409–424

    Article  Google Scholar 

  18. He L, Hannon GJ (2004) MicroRNAs small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531

    Article  PubMed  CAS  Google Scholar 

  19. Narumiya S, Tanji M, Ishizaki T (2009) Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion. Cancer Metastasis Rev 28:65–76

    Article  PubMed  CAS  Google Scholar 

  20. Liu S (2011) The ROCK signaling and breast cancer metastasis. Mol Biol Rep 38:1363–1366

    Article  PubMed  CAS  Google Scholar 

  21. Oellers P, Schroer U, Senner V, Paulus W, Thanos S (2009) ROCKs are expressed in brain tumors and are required for glioma cell migration on myelinated axons. Glia 57:499–509

    Article  PubMed  Google Scholar 

  22. Liu X, Choy E, Hornicek FJ, Yang S, Yang C, Harmon D, Mankin H, Duan Z (2011) ROCK1 as a potential therapeutic target in osteosarcoma. J Orthop Res 29:1259–1266

    Article  PubMed  CAS  Google Scholar 

  23. Kamai T, Tsujii T, Arai K, Takagi K, Asami H, Ito Y (2003) Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer. Clin Cancer Res 9:2632–2641

    PubMed  CAS  Google Scholar 

  24. Chen J, Ye L, Zhang L, Jiang WG (2008) Placenta growth factor, PLGF, influences the motility of lung cancer cells, the role of Rho associated kinase, Rock1. J Cell Biochem 105:313–320

    Article  PubMed  CAS  Google Scholar 

  25. Lin SL, Chiang A, Chang D, Ying SY (2008) Loss of mir-146a function in hormone-refractory prostate cancer. RNA 14:417–424

    Article  PubMed  CAS  Google Scholar 

  26. Ueno K, Hirata H, Shahryari V, Chen Y (2011) Tumour suppressor microRNA-584 directly targets oncogene Rock-1 and decreases invasion ability in human clear cell renal cell carcinoma. Br J Cancer 104:308–315

    Article  PubMed  CAS  Google Scholar 

  27. Li J, Song Y, Wang Y, Luo J, Yu W (2013) MicroRNA-148a suppresses epithelial-to-mesenchymal transition by targeting ROCK1 in non-small cell lung cancer cells. Mol Cell Biochem. doi:10.1007/s11010-013-1682-y

    Google Scholar 

  28. Gupta GP, Massague J (2006) Cancer metastasis: building a framework. Cell 127:679–695

    Article  PubMed  CAS  Google Scholar 

  29. Klein CA (2008) Cancer. The metastasis cascade. Science 321:1785–1787

    Article  PubMed  CAS  Google Scholar 

  30. Sreekumar R, Sayan BS, Mirnezami AH, Sayan AE (2011) MicroRNA control of invasion and metastasis pathways. Front Genet 2:58

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by National Science Foundation, Grant No. 81070688/H0726.

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The authors have no conflict of interest to disclose.

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Correspondence to Qin Fu.

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Wang, Y., Zhao, W. & Fu, Q. miR-335 suppresses migration and invasion by targeting ROCK1 in osteosarcoma cells. Mol Cell Biochem 384, 105–111 (2013). https://doi.org/10.1007/s11010-013-1786-4

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  • DOI: https://doi.org/10.1007/s11010-013-1786-4

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