Tumor Biology

, Volume 37, Issue 5, pp 5933–5940 | Cite as

The overexpression of miR-30a affects cell proliferation of chondrosarcoma via targeting Runx2

  • Dong Jiang
  • Xiaoming Zheng
  • Wei Shan
  • Ying Shan
Original Article


MicroRNAs (miRNAs) are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers. Aberrant miRNA expression has been observed in human chondrosarcoma (CS). The purpose of the present study was to evaluate the expression and molecular mechanisms of Runx2 and miR-30a in human CS tissues and CS cell lines JJ012, SW1353, and L3252. In the present study, we found that the expression of miR-30a was markedly downregulated in CS cell lines and human CS tissues, compared to matched non-tumor-associated tissues. Furthermore, miR-30a expression was inversely proportional to that of Runx2 messenger RNA (mRNA) and protein. Upregulation of miR-30a dramatically reduced the proliferation, colony formation, and cell cycle-related proteins of CS cells. Flow cytometry analysis showed that ectopic expression of miR-30a significantly decreased the percentage of S phase cells and increased the percentage of G1/G0 phase cells. Luciferase reporter assays confirmed that miR-30a binding to the 3′-untranslated region (3′-UTR) region of Runx2 inhibited the expression of Runx2 in cancer cells. Taken together, our results suggest that miR-30a plays an important role to inhibit the proliferation of CS cells and presents a novel mechanism for direct miRNA-mediated suppression of Runx2 in CS. Thus, miR-30a/Runx2 may have an important role in treatment of CS patients.


miR-30a Runx2 CS Proliferation 



We greatly thank the other members in our lab for valuable suggestions and writing. Dong Jiang conceived and designed the experiments. Dong Jiang and Xiaoming Zheng performed the experiments. Wei Shan and Ying Shan analyzed the data. Ying Shan wrote the paper.

Compliance with ethical standards

Conflict of interest



  1. 1.
    Jemal A, Siegel R, Xu J. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.CrossRefPubMedGoogle Scholar
  2. 2.
    Leddy LR, Holmes RE. Chondrosarcoma of bone. Cancer Treat Res. 2014;162:117–30.CrossRefPubMedGoogle Scholar
  3. 3.
    Frezza AM, Cesari M, Baumhoer D, Biau D, Bielack S, Campanacci DA, et al. Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study. Eur J Cancer. 2015;51:374–81.Google Scholar
  4. 4.
    Gherman V, Tomuleasa C, Bungardean C, Crisan N, Ona VD, Feciche B, et al. Management of renal extraskeletal mesenchymal chondrosarcoma. BMC Surg. 2014;14:107.Google Scholar
  5. 5.
    Guder WK, Hardes J, Gosheger G, Nottrott M, Streitbürger A. Osteosarcoma and chondrosarcoma of the pelvis and lower extremities. Chirurg. 2015;86(10):993–1004.Google Scholar
  6. 6.
    Yao M, Wang L, Yao Y, Gu HB, Yao DF. Biomarker-based microRNA therapeutic strategies for hepatocellular carcinoma. J Clin Transl Hepatol. 2014;2(4):253–8.Google Scholar
  7. 7.
    Muluhngwi P, Klinge CM. Roles for miRNAs in endocrine resistance in breast cancer. Endocr Relat Cancer. 2015;22(5):R279–300.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Kagiya T. MicroRNAs and osteolytic bone metastasis: the roles of microRNAs in tumor-induced osteoclast differentiation. J Clin Med. 2015;4(9):1741–52.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Liu H, Ren G, Zhu L, Liu X, He X. The upregulation of miRNA-146a inhibited biological behaviors of ESCC through inhibition of IRS2. Tumour Biol. 2015. doi: 10.1007/s13277-015-4274-5.
  10. 10.
    Luna-Aguirre CM, de la Luz Martinez-Fierro M, Mar-Aguilar F, Garza-Veloz I, Treviño-Alvarado V, Rojas-Martinez A, et al. Circulating microRNA expression profile in B-cell acute lymphoblastic leukemia. Cancer Biomark. 2015;15(3):299–310.Google Scholar
  11. 11.
    Sampson VB, Yoo S, Kumar A, Vetter NS, Kolb EA. MicroRNAs and potential targets in osteosarcoma: review. Front Pediatr. 2015;3:69.Google Scholar
  12. 12.
    Lv S, Sun B, Dai C, Shi R, Zhou X, Lv W, et al. The downregulation of microRNA-146a modulates TGF-β signaling pathways activity in glioblastoma. Mol Neurobiol. 2015;52(3):1257–62.Google Scholar
  13. 13.
    Wang P, Zhang N, Liang J, Li J, Han S, Li J. Micro-RNA-30a regulates ischemia-induced cell death by targeting heat shock protein HSPA5 in primary cultured cortical neurons and mouse brain after stroke. J Neurosci Res. 2015;93(11):1756–68.Google Scholar
  14. 14.
    Peng R, Zhou L, Zhou Y, Zhao Y, Li Q, Ni D, et al. MiR-30a inhibits the epithelial-mesenchymal transition of podocytes through downregulation of NFATc3. Int J Mol Sci. 2015;16(10):24032–47.Google Scholar
  15. 15.
    Tang R, Liang L, Luo D, Feng Z, Huang Q, He R, et al. Downregulation of MiR-30a is associated with poor prognosis in lung cancer. Med Sci Monit. 2015;21:2514–20.Google Scholar
  16. 16.
    van der Weyden L, Papaspyropoulos A, Poulogiannis G, Rust AG, Rashid M, Adams DJ, et al. Loss of RASSF1A synergizes with deregulated RUNX2 signaling in tumorigenesis. Cancer Res. 2012;72(15):3817–27.Google Scholar
  17. 17.
    Sase T, Suzuki T, Miura K, Shiiba K, Sato I, Nakamura Y, et al. Runt-related transcription factor 2 in human colon carcinoma: a potent prognostic factor associated with estrogen receptor. Int J Cancer. 2012;131(10):2284–93.Google Scholar
  18. 18.
    Pan Y, Zhang Y, Chen L, Liu Y, Feng Y, Yan J. The critical role of Rab31 in cell proliferation and apoptosis in cancer progression. Mol Neurobiol. 2015. doi: 10.1007/s12035-015-9378-9.
  19. 19.
    Brusgard JL, Choe M, Chumsri S, Renoud K, MacKerell AD Jr, Sudol M, et al. RUNX2 and TAZ-dependent signaling pathways regulate soluble E-Cadherin levels and tumorsphere formation in breast cancer cells. Oncotarget. 2015;6(29):28132–50.Google Scholar
  20. 20.
    Boufraqech M, Nilubol N, Zhang L, Gara SK, Sadowski SM, Mehta A, et al. miR30a inhibits LOX expression and anaplastic thyroid cancer progression. Cancer Res. 2015;75(2):367–77.Google Scholar
  21. 21.
    Tsukamoto O, Miura K, Mishima H, Abe S, Kaneuchi M, Higashijima A, et al. Identification of endometrioid endometrial carcinoma-associated microRNAs in tissue and plasma. Gynecol Oncol. 2014;132(3):715–21.Google Scholar
  22. 22.
    Yu Y, Cao L, Yang L, Kang R, Lotze M, Tang D. microRNA 30A promotes autophagy in response to cancer therapy. Autophagy. 2012;8(5):853–5.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Dong Jiang
    • 1
  • Xiaoming Zheng
    • 1
  • Wei Shan
    • 1
  • Ying Shan
    • 2
  1. 1.Department of Anatomy, College of Basic Medical SciencesLiaoning Medical UniversityJinzhouChina
  2. 2.Department of Immunology, College of Basic Medical SciencesLiaoning Medical UniversityJinzhouChina

Personalised recommendations