Tumor Biology

, Volume 35, Issue 8, pp 7645–7650 | Cite as

miR-145 inhibits osteosarcoma cells proliferation and invasion by targeting ROCK1

Research Article


MicroRNAs (miRNAs) contribute to the development and progression of various types of human cancers. The aim of this study was to study the role of miR-145 and to identify its functional target gene in osteosarcoma (OS) cells. We found that miR-145 was reduced in OS tissues and cell lines. Enforced expression of miR-145 inhibited cell proliferation, migration, and invasion abilities of MG-63 cells. Furthermore, we revealed that Rho-associated protein kinase 1 (ROCK1) was a target of miR-145 in OS. Finally, we found that silencing of ROCK1 performed similar effects with miR-145 in MG-63 cells, and ROCK1 was inversely correlated with miR-145 in OS tissues. Collectively, these data indicate that miR-145 may act as a tumor suppressor and contributes to the progression of OS through targeting ROCK1.


Osteosarcoma miR-145 ROCK1 Proliferation Invasion 


Conflicts of interest



  1. 1.
    Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2009;152:3–13.PubMedCrossRefGoogle Scholar
  2. 2.
    Ando K, Heymann MF, Stresing V, Mori K, Redini F, Heymann D. Current therapeutic strategies and novel approaches in osteosarcoma. Cancers. 2013;5:591–616.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Sun K, Lai EC. Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013;14:535–48.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Chou J, Shahi P, Werb Z. MicroRNA-mediated regulation of the tumor microenvironment. Cell Cycle. 2013;12:3262–71.PubMedCrossRefGoogle Scholar
  5. 5.
    Gao Y, Luo LH, Li S, Yang C. miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression. Biochem Biophys Res Commun. 2014;444:230–4.PubMedCrossRefGoogle Scholar
  6. 6.
    Song QC, Shi ZB, Zhang YT, Ji L, Wang KZ, Duan DP, et al. Downregulation of microRNA-26a is associated with metastatic potential and the poor prognosis of osteosarcoma patients. Oncol Rep. 2014;31:1263–70.PubMedGoogle Scholar
  7. 7.
    Tang M, Lin L, Cai H, Tang J, Zhou Z. MicroRNA-145 downregulation associates with advanced tumor progression and poor prognosis in patients suffering osteosarcoma. Onco Targets Ther. 2013;6:833–8.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Xu JQ, Liu P, Si MJ, Ding XY. MicroRNA-126 inhibits osteosarcoma cells proliferation by targeting Sirt1. Tumour Biol. 2013;34:3871–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Feng Y, Zhu J, Ou C, Deng Z, Chen M, Huang W, et al. MicroRNA-145 inhibits tumour growth and metastasis in colorectal cancer by targeting fascin-1. Br J Cancer. 2014;110:2300–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Qiu T, Zhou X, Wang J, Du Y, Xu J, Huang Z, et al. MiR-145, miR-133a and miR-133b inhibit proliferation, migration, invasion and cell cycle progression via targeting transcription factor Sp1 in gastric cancer. FEBS Lett. 2014;588:1168–77.PubMedCrossRefGoogle Scholar
  11. 11.
    Xin C, Zhang H, Liu Z. miR-154 suppresses colorectal cancer cell growth and motility by targeting TLR2. Mol Cell Biochem. 2014;387:271–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Zhao H, Wang Y, Yang L, Jiang R, Li W. MiR-25 promotes gastric cancer cells growth and motility by targeting RECK. Mol Cell Biochem. 2014;385:207–13.PubMedCrossRefGoogle Scholar
  13. 13.
    Chen B, Huang T, Jiang J, Lv L, Li H, Xia S. miR-141 suppresses proliferation and motility of gastric cancer cells by targeting HDGF. Mol Cell Biochem. 2014;388:211–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Zhou X, Gao Q, Wang J, Zhang X, Liu K, Duan Z. Linc-RNA-RoR acts as a “sponge” against mediation of the differentiation of endometrial cancer stem cells by microRNA-145. Gynecol Oncol. 2014;133:333–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Guo YH, Zhang C, Shi J, Xu MH, Liu F, Yuan HH, et al. Abnormal activation of the EGFR signaling pathway mediates the downregulation of miR-145 through the ERK1/2 in non-small cell lung cancer. Oncol Rep. 2014;31:1940–6.PubMedGoogle Scholar
  16. 16.
    Mirgani MT, Isacchi B, Sadeghizadeh M, Marra F, Bilia AR, Mowla SJ, et al. Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells. Int J Nanomedicine. 2014;9:403–17.Google Scholar
  17. 17.
    Zhu X, Li Y, Xie C, Yin X, Liu Y, Cao Y, Fang Y, Lin X, Xu Y, Xu W, Shen H, Wen J: miR-145 sensitizes ovarian cancer cells to paclitaxel by targeting Sp1 and Cdk6. International Journal of Cancer 2014; doi:  10.1002/ijc.28774.
  18. 18.
    Lu R, Ji Z, Li X, Zhai Q, Zhao C, Jiang Z, et al. miR-145 functions as tumor suppressor and targets two oncogenes, ANGPT2 and NEDD9, in renal cell carcinoma. J Cancer Res Clin Oncol. 2014;140:387–97.PubMedCrossRefGoogle Scholar
  19. 19.
    Wang F, Xia J, Wang N, Zong H. miR-145 inhibits proliferation and invasion of esophageal squamous cell carcinoma in part by targeting c-Myc. Onkologie. 2013;36:754–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Fan L, Wu Q, Xing X, Wei Y, Shao Z. MicroRNA-145 targets vascular endothelial growth factor and inhibits invasion and metastasis of osteosarcoma cells. Acta Biochim Biophys Sin. 2012;44:407–14.PubMedCrossRefGoogle Scholar
  21. 21.
    Schofield AV, Bernard O. Rho-associated coiled-coil kinase (ROCK) signaling and disease. Crit Rev Biochem Mol Biol. 2013;48:301–16.PubMedCrossRefGoogle Scholar
  22. 22.
    An L, Liu Y, Wu A, Guan Y. microRNA-124 inhibits migration and invasion by down-regulating ROCK1 in glioma. PLoS One. 2013;8:e69478.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Zhang C, Zhang S, Zhang Z, He J, Xu Y, Liu S: ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc. Oncogene 2013; doi:  10.1038/onc.2013.505.
  24. 24.
    Wang Y, Zhao W, Fu Q. miR-335 suppresses migration and invasion by targeting ROCK1 in osteosarcoma cells. Mol Cell Biochem. 2013;384:105–11.PubMedCrossRefGoogle Scholar
  25. 25.
    Shin JY, Kim YI, Cho SJ, Lee MK, Kook MC, Lee JH, et al. MicroRNA 135a suppresses lymph node metastasis through down-regulation of ROCK1 in early gastric cancer. PLoS One. 2014;9:e85205.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Gu X, Meng S, Liu S, Jia C, Fang Y, Li S, et al. miR-124 represses ROCK1 expression to promote neurite elongation through activation of the PI3K/Akt signal pathway. J Mol Neurosci. 2014;52:156–65.PubMedCrossRefGoogle Scholar
  27. 27.
    Zhou X, Wei M, Wang W. MicroRNA-340 suppresses osteosarcoma tumor growth and metastasis by directly targeting ROCK1. Biochem Biophys Res Commun. 2013;437:653–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Wan X, Cheng Q, Peng R, Ma Z, Chen Z, Cao Y, et al. ROCK1, a novel target of miR-145, promotes glioma cell invasion. Mol Med Rep. 2014;9:1877–82.PubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Enqi Li
    • 1
  • Jinli Zhang
    • 1
  • Tianxiang Yuan
    • 1
  • Baotong Ma
    • 1
  1. 1.Department of Orthopaedic TraumaTianJin HospitalTianjinChina

Personalised recommendations