Skip to main content

Advertisement

SpringerLink
Log in

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

  • Research Article
  • Published:
Tumor Biology

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Ando K, Heymann MF, Stresing V, et al. Current therapeutic strategies and novel approaches in osteosarcoma. Cancers (Basel). 2013;5(2):591–616.

    Article  CAS  Google Scholar 

  2. Sun K, Lai EC. Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013;14(8):535–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol. 2013;14(8):475–88.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chou J, Shahi P, Werb Z. microRNA-mediated regulation of the tumor microenvironment. Cell Cycle. 2013;12(20):3262–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  7. Pencheva N, Tavazoie SF. Control of metastatic progression by microRNA regulatory networks. Nat Cell Biol. 2013;15(6):546–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Li J, Lu X. The emerging roles of 3′untranslated regions in cancer. Cancer Lett. 2013;337(1):22–5.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Ogata-Kawata H, Izumiya M, Kurioka D, et al. Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One. 2014;9(4):e92921.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  18. Hu X, Chen D, Cui Y, et al. Targeting microRNA-23a to inhibit glioma cell invasion via HOXD10. Sci Rep. 2013;3:3423.

    PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  25. Tattermusch A, Brockdorff N. A scaffold for X chromosome inactivation. 2011;130(2):247–53.

  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.

    Article  CAS  PubMed  Google Scholar 

  27. Seo J, Lozano MM, Dudley JP. Nuclear matrix binding regulates SATB1-mediated transcriptional repression. J Biol Chem. 2005;280(26):24600–9.

    Article  CAS  PubMed  Google Scholar 

  28. Shannon MF. A nuclear address with influence. Nat Genet. 2003;34(1):4–6.

    Article  CAS  PubMed  Google Scholar 

  29. Cai S, Han HJ, Kohwi-Shigematsu T. Tissue-specific nuclear architecture and gene expression regulated by SATB1. 2003;34(1):42–51.

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

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

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, 110004, Liaoning, China

    Guangbin Wang, Bin Li, Yonghui Fu, Ming He, Jiashi Wang, Peng Shen & Lunhao Bai

Authors
  1. Guangbin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yonghui Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ming He
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiashi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peng Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lunhao Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lunhao Bai.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, G., Li, B., Fu, Y. et al. miR-23a suppresses proliferation of osteosarcoma cells by targeting SATB1. Tumor Biol. 36, 4715–4721 (2015). https://doi.org/10.1007/s13277-015-3120-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-3120-0

Keywords

Search

Navigation