Tumor Biology

, Volume 36, Issue 6, pp 4715–4721 | Cite as

miR-23a suppresses proliferation of osteosarcoma cells by targeting SATB1

  • Guangbin Wang
  • Bin Li
  • Yonghui Fu
  • Ming He
  • Jiashi Wang
  • Peng Shen
  • Lunhao Bai
Research Article


Accumulating evidence has shown that microRNAs are involved in multiple processes in cancer development and progression. Recent studies have shown that miR-23a functions as an oncogene in various human cancer types, but its role in osteosarcoma remains poorly understood. Here, we demonstrated that miR-23a is frequently downregulated in osteosarcoma specimens and cell lines compared with adjacent noncancerous tissues and cell line. Bioinformatics analysis further revealed SATB1 as a potential target of miR-23a. Data from luciferase reporter assays showed that miR-23a directly binds to the 3′UTR of SATB1 messenger RNA (mRNA). Furthermore, we found that expression patterns of miR-23a were inversely correlated with those of SATB1 in osteosarcoma tissues and cell lines, and overexpression of miR-23a suppressed SATB1 expression at both transcriptional and translational levels in osteosarcoma cell lines. In functional assays, miR-23a inhibited osteosarcoma cell proliferation, which could be reversed by overexpression of SATB1. Furthermore, knockdown of SATB1 reduced osteosarcoma cell proliferation, which resembled the inhibitory effects of miR-23a overexpression. Taken together, our data provide compelling evidence that miR-23a functions as a tumor suppressor in osteosarcoma, and its inhibitory effect on tumor are mediated chiefly through downregulation of SATB1.


miR-23a Osteosarcoma Proliferation SATB1 



This work was supported by National Science Foundation (Grant No. 81300714/H0726).

Conflicts of interest



  1. 1.
    Ando K, Heymann MF, Stresing V, et al. Current therapeutic strategies and novel approaches in osteosarcoma. Cancers (Basel). 2013;5(2):591–616.CrossRefGoogle Scholar
  2. 2.
    Sun K, Lai EC. Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013;14(8):535–48.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol. 2013;14(8):475–88.CrossRefPubMedGoogle Scholar
  4. 4.
    Kasinski AL, Slack FJ. Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 2011;11(12):849–64.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Chou J, Shahi P, Werb Z. microRNA-mediated regulation of the tumor microenvironment. Cell Cycle. 2013;12(20):3262–71.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Sandoval J, Peiró-Chova L, Pallardó FV, et al. Epigenetic biomarkers in laboratory diagnostics: emerging approaches and opportunities. Expert Rev Mol Diagn. 2013;13(5):457–71.CrossRefPubMedGoogle Scholar
  7. 7.
    Pencheva N, Tavazoie SF. Control of metastatic progression by microRNA regulatory networks. Nat Cell Biol. 2013;15(6):546–54.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Li J, Lu X. The emerging roles of 3′untranslated regions in cancer. Cancer Lett. 2013;337(1):22–5.CrossRefPubMedGoogle Scholar
  9. 9.
    Fujita PA, Rhead B, Zweig AS, et al. The UCSC Genome Browser database: update 2011. Nucleic Acids Res. 2011;39(Database issue):D876–82.CrossRefPubMedGoogle Scholar
  10. 10.
    Huang S, He X, Ding J, et al. Upregulation of miR-23a approximately 27a approximately 24 decreases transforming growth factor-beta-induced tumor-suppressive activities in human hepatocellular carcinoma cells. Int J Cancer. 2008;123(4):972–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Mertens-Talcott SU, Chintharlapalli S, Li X, et al. The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. 2007;67(22):11001–11.Google Scholar
  12. 12.
    Lal A, Pan Y, Navarro F, et al. miR-24-mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells. Nat Struct Mol Biol. 2009;16(5):492–8.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lin Z, Murtaza I, Wang K, et al. miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy. Proc Natl Acad Sci U S A. 2009;106(29):12103–8.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Chhabra R, Dubey R, Saini N. Cooperative and individualistic functions of the microRNAs in the miR-23a * 27a * 24–2 cluster and its implication in human diseases. 2010;9:232.Google Scholar
  15. 15.
    Cao M, Seike M, Soeno C, et al. MiR-23a regulates TGF-β-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells. Int J Oncol. 2012;41(3):869–75.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Ogata-Kawata H, Izumiya M, Kurioka D, et al. Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One. 2014;9(4):e92921.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Bao L, Zhao J, Dai X, et al. Correlation between miR-23a and onset of hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 2014;38(3):318–30.CrossRefPubMedGoogle Scholar
  18. 18.
    Hu X, Chen D, Cui Y, et al. Targeting microRNA-23a to inhibit glioma cell invasion via HOXD10. Sci Rep. 2013;3:3423.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Li X, Liu X, Xu W, et al. c-MYC-regulated miR-23a/24-2/27a cluster promotes mammary carcinoma cell invasion and hepatic metastasis by targeting Sprouty2. J Biol Chem. 2013;288(25):18121–33.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Wang Z, Wei W, Sarkar FH. miR-23a, a critical regulator of “migR”ation and metastasis in colorectal cancer. Cancer Discov. 2012;2(6):489–91.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Zhu LH, Liu T, Tang H, et al. MicroRNA-23a promotes the growth of gastric adenocarcinoma cell line MGC803 and downregulates interleukin-6 receptor. FEBS J. 2010;277(18):3726–34.CrossRefPubMedGoogle Scholar
  22. 22.
    Wang WL, Yang C, Han XL, et al. MicroRNA-23a expression in paraffin-embedded specimen correlates with overall survival of diffuse large B-cell lymphoma. Med Oncol. 2014;31(4):919.CrossRefPubMedGoogle Scholar
  23. 23.
    He Y, Meng C, Shao Z, et al. MiR-23a functions as a tumor suppressor in osteosarcoma. Cell Physiol Biochem. 2014;34(5):1485–96.CrossRefPubMedGoogle Scholar
  24. 24.
    Dickinson LA, Joh T, Kohwi Y, et al. A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition. Cell. 1992;70(4):631–45.CrossRefPubMedGoogle Scholar
  25. 25.
    Tattermusch A, Brockdorff N. A scaffold for X chromosome inactivation. 2011;130(2):247–53.Google Scholar
  26. 26.
    Yamaguchi H, Tateno M, Yamasaki K. Solution structure and DNA-binding mode of the matrix attachment region-binding domain of the transcription factor SATB1 that regulates the T-cell maturation. J Biol Chem. 2006;281(8):5319–27.CrossRefPubMedGoogle Scholar
  27. 27.
    Seo J, Lozano MM, Dudley JP. Nuclear matrix binding regulates SATB1-mediated transcriptional repression. J Biol Chem. 2005;280(26):24600–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Shannon MF. A nuclear address with influence. Nat Genet. 2003;34(1):4–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Cai S, Han HJ, Kohwi-Shigematsu T. Tissue-specific nuclear architecture and gene expression regulated by SATB1. 2003;34(1):42–51.Google Scholar
  30. 30.
    Han HJ, Russo J, Kohwi Y, et al. SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature. 2008;452(7184):187–93.CrossRefPubMedGoogle Scholar
  31. 31.
    Meng WJ, Yan H, Zhou B, et al. Correlation of SATB1 over-expression with the progression of human rectal cancer. Int J Colorectal Dis. 2011;27(2):143–50.CrossRefPubMedGoogle Scholar
  32. 32.
    Zhang Y, Tian X, Ji H, et al. Expression of SATB1 promotes the growth and metastasis of colorectal cancer. PLoS One. 2014;9(6):e100413.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Tu W, Luo M, Wang Z, et al. Upregulation of SATB1 promotes tumor growth and metastasis in liver cancer. Liver Int. 2012;32(7):1064–78.CrossRefPubMedGoogle Scholar
  34. 34.
    Cheng C, Wan F, Liu L, et al. Overexpression of SATB1 is associated with biologic behavior in human renal cell carcinoma. PLoS One. 2014;9(5):e97406.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Han B, Luan L, Xu Z, et al. Expression and biological roles of SATB1 in human bladder cancer. Tumour Biol. 2013;34(5):2943–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Mao L, Yang C, Wang J, et al. SATB1 is overexpressed in metastatic prostate cancer and promotes prostate cancer cell growth and invasion. J Transl Med. 2013;11:111.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Zhang H, Su X, Guo L, et al. Silencing SATB1 inhibits the malignant phenotype and increases sensitivity of human osteosarcoma U2OS cells to arsenic trioxide. Int J Med Sci. 2014;11(12):1262–9.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Zhang H, Qu S, Li S, et al. Silencing SATB1 inhibits proliferation of human osteosarcoma U2OS cells. Mol Cell Biochem. 2013;378(1–2):39–45.CrossRefPubMedGoogle Scholar
  39. 39.
    Nagpal N, Ahmad HM, Molparia B, et al. MicroRNA-191, an estrogen-responsive microRNA, functions as an oncogenic regulator in human breast cancer. Carcinogenesis. 2013;34(8):1889–99.CrossRefPubMedGoogle Scholar
  40. 40.
    Di Leva G, Piovan C, Gasparini P, et al. Estrogen mediated-activation of miR-191/425 cluster modulates tumorigenicity of breast cancer cells depending on estrogen receptor status. PLoS Genet. 2013;9(3):e1003311.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Elton TS, Selemon H, Elton SM, et al. Regulation of the MIR155 host gene in physiological and pathological processes. Gene. 2013;532(1):1–12.CrossRefPubMedGoogle Scholar
  42. 42.
    Lena AM, Mancini M, Rivetti di Val Cervo P, et al. MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation. Biochem Biophys Res Commun. 2012;423(3):509–14.CrossRefPubMedGoogle Scholar
  43. 43.
    Yang S, Banerjee S, Freitas A, et al. miR-21 regulates chronic hypoxia-induced pulmonary vascular remodeling. Am J Physiol Lung Cell Mol Physiol. 2012;302(6):L521–9.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    McInnes N, Sadlon TJ, Brown CY, et al. FOXP3 and FOXP3-regulated microRNAs suppress SATB1 in breast cancer cells. Oncogene. 2012;31(8):1045–54.CrossRefPubMedGoogle Scholar
  45. 45.
    Li QQ, Chen ZQ, Cao XX, et al. Involvement of NF-κB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial-mesenchymal transition of breast cancer cells. Cell Death Differ. 2011;18(1):16–25.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Guangbin Wang
    • 1
  • Bin Li
    • 1
  • Yonghui Fu
    • 1
  • Ming He
    • 1
  • Jiashi Wang
    • 1
  • Peng Shen
    • 1
  • Lunhao Bai
    • 1
  1. 1.Department of Orthopedics, Shengjing HospitalChina Medical UniversityShenyangChina

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