Skip to main content

Advertisement

Log in

MiR-21 up-regulation mediates glioblastoma cancer stem cells apoptosis and proliferation by targeting FASLG

Molecular Biology Reports Aims and scope Submit manuscript

Abstract

To investigate whether miR-21 can affect the apoptosis and proliferation of glioblastoma cancer stem cells (GSCs) from down-regulating FASLG. The expression of miRNA-21 was detected by quantitative real-time PCR in normal brain tissue and glioblastoma samples, and the changes of miRNA-21 expression between GSCs and non-GSCs were also detected. The apoptosis and proliferation ability of miR-21 in GSCs were analyzed by MTT and flow cytometry assay after anti-miR-21 transfection. For the regulation mechanism analysis of miR-21, TargetScan, PicTar and microRNA were selected to predict some potential target genes of miR-21. The predicted gene was identified to be the direct and specific target gene of miR-21 by luciferase activities assay and western blot. RNA interference technology was used to confirm the apoptosis and proliferation effects of miR-21 were directly induced by FASLG. The expression of miR-21 increased significantly in glioblastoma contrast to normal brain tissue, and miR-21 up-regulated in GSCs remarkably. The proliferation of GSCs cell could be inhibited with high-expression of miR-21 and this effect could be restored by miR-21 knocked down. Mechanism analysis revealed that FASLG was a specific and direct target gene of miR-21. The advanced effects of anti-miR-21 on GSCs apoptosis and proliferation were mediated by expression of silenced FASLG. In summary, aberrantly expressed miR-21 regulates GSCs apoptosis and proliferation partly through directly down-regulating FASLG protein expression in GSCs and this might offer a new potential therapeutic stratagem for glioblastoma.

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

Access this article

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

References

  1. Kuhnt D, Becker A, Ganslandt O, Bauer M, Buchfelder M, Nimsky C (2011) Correlation of the extent of tumor volume resection and patient survival in surgery of glioblastoma multiforme with high-field intraoperative MRI guidance. Neuro Oncol 13(12):1339–1348

    Article  PubMed Central  PubMed  Google Scholar 

  2. Wang S, Huang S, Zhao X, Zhang Q, Wu M, Sun F, Han G, Wu D (2013) Enrichment of prostate cancer stem cells from primary prostate cancer cultures of biopsy samples. Int J Clin Exp Pathol 7(1):184–193

    PubMed Central  PubMed  Google Scholar 

  3. Morihiro Y, Yasumoto Y, Vaidyan LK, Sadahiro H, Uchida T, Inamura A, Sharifi K, Ideguchi M, Nomura S, Tokuda N, Kashiwabara S, Ishii A, Ikeda E, Owada Y, Suzuki M (2013) Fatty acid binding protein 7 as a marker of glioma stem cells. Pathol Int 63(11):546–553

    Article  CAS  PubMed  Google Scholar 

  4. Sato A, Okada M, Shibuya K, Watanabe E, Seino S, Narita Y, Shibui S, Kayama T, Kitanaka C (2014) Pivotal role for ROS activation of p38 MAPK in the control of differentiation and tumor-initiating capacity of glioma-initiating cells. Stem Cell Res 12(1):119–131

    Article  CAS  PubMed  Google Scholar 

  5. Wu L, Li G, Feng D, Qin H, Gong L, Zhang J, Zhang Z (2013) MicroRNA-21 expression is associated with overall survival in patients with glioma. Diagn Pathol 8(1):200

    Article  PubMed Central  PubMed  Google Scholar 

  6. Xiong B, Cheng Y, Ma L, Zhang C (2013) MiR-21 regulates biological behavior through the PTEN/PI-3K/Akt signaling pathway in human colorectal cancer cells. Int J Oncol 42(1):219–228

    CAS  PubMed  Google Scholar 

  7. Zhang W, Bai W, Zhang W (2013) MiR-21 suppresses the anticancer activities of curcumin by targeting PTEN gene in human non-small cell lung cancer A549 cells. Clin Transl Oncol 16(8):708–713

  8. Kawakita A, Yanamoto S, Yamada SI, Naruse T, Takahashi H, Kawasaki G, Umeda M (2013) MicroRNA-21 promotes oral cancer invasion via the Wnt/β-catenin pathway by targeting DKK2. Pathol Oncol Res 20:253–261

    Article  Google Scholar 

  9. Rich JN, Eyler CE (2008) Cancer stem cells in brain tumor biology. Cold Spring Harb Symp Quant Biol 73:411–420

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Jin X, Jin X, Jung JE, Beck S, Kim H (2013) Cell surface Nestin is a biomarker for glioma stem cells. Biochem Biophys Res Commun 433(4):496–501

    Article  CAS  PubMed  Google Scholar 

  11. Sato A, Okada M, Shibuya K, Watanabe E, Seino S, Narita Y, Shibui S, Kayama T, Kitanaka C (2014) Pivotal role for ROS activation of p38 MAPK in the control of differentiation and tumor-initiating capacity of glioma-initiating cells. Stem Cell Res 12(1):119–131

    Article  CAS  PubMed  Google Scholar 

  12. Sampetrean O, Saya H (2013) Characteristics of glioma stem cells. Brain Tumor Pathol 30(4):209–214

    Article  CAS  PubMed  Google Scholar 

  13. Lim HY, Kim KM, Kim BK, Shim JK, Lee JH, Huh YM, Kim SH, Kim EH, Park EK, Shim KW, Chang JH, Kim DS, Kim SH, Hong YK, Lee SJ, Kang SG (2013) Isolation of mesenchymal stem-like cells in meningioma specimens. Int J Oncol 43(4):1260–1268

    CAS  PubMed  Google Scholar 

  14. Vescovi AL, Galli R, Reynolds BA (2006) Brain tumour stem cells. Nat Rev Cancer 6(6):425–436

    Article  CAS  PubMed  Google Scholar 

  15. Hong X, Chedid K, Kalkanis SN (2012) Glioblastoma cell line-derived spheres in serum-containing medium versus serum-free medium: a comparison of cancer stem cell properties. Int J Oncol 41(5):1693–1700

    CAS  PubMed  Google Scholar 

  16. Li M, Li J, Liu L, Li W, Yang Y, Yuan J (2013) MicroRNA in Human Glioma. Cancers (Basel). 5(4):1306–1331

    Article  PubMed Central  PubMed  Google Scholar 

  17. Tu Y, Gao X, Li G, Fu H, Cui D, Liu H, Jin W, Zhang Y (2013) MicroRNA-218 inhibits glioma invasion, migration, proliferation, and cancer stem-like cell self-renewal by targeting the polycomb group gene Bmi1. Cancer Res 73(19):6046–6055

    Article  CAS  PubMed  Google Scholar 

  18. Oh JS, Kim JJ, Byun JY, Kim IA (2010) Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-Ras. Int J Radiat Oncol Biol Phys 76(1):5–8

    Article  CAS  PubMed  Google Scholar 

  19. Shen J, Wan R, Hu G, Yang L, Xiong J, Wang F, Shen J, He S, Guo X, Ni J, Guo C, Wang X (2012) miR-15b and miR-16 induce the apoptosis of rat activated pancreatic stellate cells by targeting Bcl-2 in vitro. Pancreatology 12(2):91–99

    Article  CAS  PubMed  Google Scholar 

  20. Yao Y, Li L, Huang X, Gu X, Xu Z, Zhang Y, Huang L, Li S, Dai Z, Li C, Zhou T, Cai W, Yang Z, Gao G, Yang X (2013) SERPINA3 K induces apoptosis in human colorectal cancer cells via activating the Fas/FasL/caspase-8 signaling pathway. FEBS J 280(14):3244–3255

    Article  CAS  PubMed  Google Scholar 

  21. Liu WH, Chang LS (2011) Fas/FasL-dependent and -independent activation of caspase-8 in doxorubicin-treated human breast cancer MCF-7 cells: ADAM10 down-regulation activates Fas/FasL signaling pathway. Int J Biochem Cell Biol 43(12):1708–1719

    Article  CAS  PubMed  Google Scholar 

  22. Wang WZ, Li L, Liu MY, Jin XB, Mao JW, Pu QH, Meng MJ, Chen XG, Zhu JY (2013) Curcumin induces FasL-related apoptosis through p38 activation in human hepatocellular carcinoma Huh7 cells. Life Sci 92(6–7):352–358

    CAS  PubMed  Google Scholar 

  23. Yao Y, Li L, Huang X, Gu X, Xu Z, Zhang Y, Huang L, Li S, Dai Z, Li C, Zhou T, Cai W, Yang Z, Gao G, Yang X (2013) SERPINA3K induces apoptosis in human colorectal cancer cells via activating the Fas/FasL/caspase-8 signaling pathway. FEBS J 280(14):3244–3255

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Nature Science Foundation of China (81172408, 81301862, 81172197, 81272716).

Competing interests

All authors announce that there are not competing interests between them.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yi-xue Xue.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shang, C., Guo, Y., Hong, Y. et al. MiR-21 up-regulation mediates glioblastoma cancer stem cells apoptosis and proliferation by targeting FASLG. Mol Biol Rep 42, 721–727 (2015). https://doi.org/10.1007/s11033-014-3820-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3820-3

Keywords

Navigation