Skip to main content

Advertisement

SpringerLink
Log in

MiR-210-3p Inhibits Proliferation and Migration of C6 Cells by Targeting Iscu

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Glioma is the most common primary brain tumor and the most malignant type of glioma is glioblastoma with the character of high mortality, high recurrence rate and poor prognosis. MicroRNAs act as an important component in glioma development and thus may be a potential target for the treatment of glioma. There were some researches indicated that miR-210-3p played a role in glioma development, but if it can inhibit glioma growth, as well as the underlying mechanism, is still uncertain. In the present study, we investigated the effects of miR-210-3p and its potential target gene Iscu on glioma (C6) cells proliferation and migration in vitro as well as the influence of miR-210-3p on glioma growth in vivo. The results showed that miR-210-3p inhibited the proliferation and migration of C6 cells by regulating the expression of its target gene Iscu in vitro. We also demonstrated that glioma growth was suppressed in immunodeficient mice when they were implanted with C6 cells overexpressing miR-210-3p. Our data indicated that miR-210-3p played an important role in the prevention of glioma growth by targeting Iscu and so miR-210-3p/Iscu axis might be a potential target for the treatment of glioma.

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
Fig. 6

Similar content being viewed by others

References

  1. Ricard D, Idbaih A, Ducray F, Lahutte M, Hoang-Xuan K, Delattre JY (2012) Primary brain tumours in adults. Lancet 379:1984–1996

    Article  Google Scholar 

  2. Zheng SQ, Qi Y, Wu J, Zhou FL, Yu H, Li L, Yu B, Chen XF, Zhang W (2019) CircPCMTD1 Acts as the sponge of miR-224-5p to promote glioma progression. Front Oncol 9:398

    Article  Google Scholar 

  3. Jiang T, Mao Y, Ma W, Mao Q, You Y, Yang X, Jiang C, Kang C, Li X, Chen L, Qiu X, Wang W, Li W, Yao Y, Li S, Li S, Wu A, Sai K, Bai H, Li G, Chen B, Yao K, Wei X, Liu X, Zhang Z, Dai Y, Lv S, Wang L, Lin Z, Dong J, Xu G, Ma X, Cai J, Zhang W, Wang H, Chen L, Zhang C, Yang P, Yan W, Liu Z, Hu H, Chen J, Liu Y, Yang Y, Wang Z, Wang Z, Wang Y, You G, Han L, Bao Z, Liu Y, Wang Y, Fan X, Liu S, Liu X, Wang Y, Wang Q, Chinese Glioma Cooperative G (2016) CGCG clinical practice guidelines for the management of adult diffuse gliomas. Cancer Lett 375:263–273

    Article  CAS  Google Scholar 

  4. Watkins S, Sontheimer H (2012) Unique biology of gliomas: challenges and opportunities. Trends Neurosci 35:546–556

    Article  CAS  Google Scholar 

  5. Hanaei S, Afshari K, Hirbod-Mobarakeh A, Mohajer B, Amir Dastmalchi D, Rezaei N (2018) Therapeutic efficacy of specific immunotherapy for glioma: a systematic review and meta-analysis. Rev Neurosci 29:443–461

    Article  CAS  Google Scholar 

  6. Chen Y, Huang H, Yao C, Su F, Guan W, Yan S, Ni Z (2016) Antitumor activity of combined endostatin and thymidine kinase gene therapy in C6 glioma models. Cancer Med 5:2477–2486

    Article  CAS  Google Scholar 

  7. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  Google Scholar 

  8. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854

    Article  CAS  Google Scholar 

  9. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403:901–906

    Article  CAS  Google Scholar 

  10. Esteller M (2011) Non-coding RNAs in human disease. Nat Rev Genet 12:861–874

    Article  CAS  Google Scholar 

  11. Iorio MV, Croce CM (2012) MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics A comprehensive review. EMBO Mol Med 4:143–159

    Article  CAS  Google Scholar 

  12. Liu CA, Chang CY, Hsueh KW, Su HL, Chiou TW, Lin SZ, Harn HJ (2018) Migration/invasion of malignant gliomas and implications for therapeutic treatment. Int J Mol Sci 19:E1115

    Article  Google Scholar 

  13. Tumilson CA, Lea RW, Alder JE, Shaw L (2014) Circulating microRNA biomarkers for glioma and predicting response to therapy. Mol Neurobiol 50:545–558

    Article  CAS  Google Scholar 

  14. Rupaimoole R, Slack FJ (2017) MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 16:203–222

    Article  CAS  Google Scholar 

  15. Gomez Zubieta DM, Hamood MA, Beydoun R, Pall AE, Kondapalli KC (2017) MicroRNA-135a regulates NHE9 to inhibit proliferation and migration of glioblastoma cells. Cell Commun Signal 15:55

    Article  Google Scholar 

  16. Shu M, Zheng X, Wu S, Lu H, Leng T, Zhu W, Zhou Y, Ou Y, Lin X, Lin Y, Xu D, Zhou Y, Yan G (2011) Targeting oncogenic miR-335 inhibits growth and invasion of malignant astrocytoma cells. Mol Cancer 10:59

    Article  CAS  Google Scholar 

  17. Stojcheva N, Schechtmann G, Sass S, Roth P, Florea AM, Stefanski A, Stuhler K, Wolter M, Muller NS, Theis FJ, Weller M, Reifenberger G, Happold C (2016) MicroRNA-138 promotes acquired alkylator resistance in glioblastoma by targeting the Bcl-2-interacting mediator BIM. Oncotarget 7:12937–12950

    Article  Google Scholar 

  18. Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris AL, Gleadle JM, Ragoussis J (2008) hsa-miR-210 Is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res 14:1340–1348

    Article  CAS  Google Scholar 

  19. Ho AS, Huang X, Cao H, Christman-Skieller C, Bennewith K, Le QT, Koong AC (2010) Circulating miR-210 as a novel hypoxia marker in pancreatic cancer. Transl Oncol 3:109–113

    Article  Google Scholar 

  20. Malzkorn B, Wolter M, Liesenberg F, Grzendowski M, Stuhler K, Meyer HE, Reifenberger G (2010) Identification and functional characterization of microRNAs involved in the malignant progression of gliomas. Brain Pathol 20:539–550

    Article  CAS  Google Scholar 

  21. Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, Story M, Le QT, Giaccia AJ (2009) Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation. Mol Cell 35:856–867

    Article  CAS  Google Scholar 

  22. Zong WX, Rabinowitz JD, White E (2016) Mitochondria and Cancer. Mol Cell 61:667–676

    Article  CAS  Google Scholar 

  23. Rouault TA, Tong WH (2008) Iron-sulfur cluster biogenesis and human disease. Trends Genet 24:398–407

    Article  CAS  Google Scholar 

  24. McCormick RI, Blick C, Ragoussis J, Schoedel J, Mole DR, Young AC, Selby PJ, Banks RE, Harris AL (2013) miR-210 is a target of hypoxia-inducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis. Br J Cancer 108:1133–1142

    Article  CAS  Google Scholar 

  25. Bush NA, Chang SM, Berger MS (2017) Current and future strategies for treatment of glioma. Neurosurg Rev 40:1–14

    Article  Google Scholar 

  26. Ahir BK, Ozer H, Engelhard HH, Lakka SS (2017) MicroRNAs in glioblastoma pathogenesis and therapy: a comprehensive review. Crit Rev Oncol Hematol 120:22–33

    Article  Google Scholar 

  27. Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105

    Article  CAS  Google Scholar 

  28. Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N (2005) Combinatorial microRNA target predictions. Nat Genet 37:495–500

    Article  CAS  Google Scholar 

  29. Shenouda SK, Alahari SK (2009) MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev 28:369–378

    Article  CAS  Google Scholar 

  30. Lee D, Sun S, Zhang XQ, Zhang PD, Ho AS, Kiang KM, Fung CF, Lui WM, Leung GK (2015) MicroRNA-210 and endoplasmic reticulum chaperones in the regulation of chemoresistance in glioblastoma. J Cancer 6:227–232

    Article  CAS  Google Scholar 

  31. Chen Z, Li Y, Zhang H, Huang P, Luthra R (2010) Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene 29:4362–4368

    Article  CAS  Google Scholar 

  32. Liu S, Jiang T, Zhong Y, Yu Y (2019) miR-210 inhibits cell migration and invasion by targeting the brain-derived neurotrophic factor in glioblastoma. J Cell Biochem. https://doi.org/10.1002/jcb.28414

    Article  PubMed  PubMed Central  Google Scholar 

  33. Zhang S, Lai N, Liao K, Sun J, Lin Y (2015) MicroRNA-210 regulates cell proliferation and apoptosis by targeting regulator of differentiation 1 in glioblastoma cells. Folia Neuropathol 53:236–244

    Article  Google Scholar 

  34. Shang C, Hong Y, Guo Y, Liu YH, Xue YX (2014) MiR-210 up-regulation inhibits proliferation and induces apoptosis in glioma cells by targeting SIN3A. Med Sci Monit 20:2571–2577

    Article  CAS  Google Scholar 

  35. Lavon I, Zrihan D, Granit A, Einstein O, Fainstein N, Cohen MA, Cohen MA, Zelikovitch B, Shoshan Y, Spektor S, Reubinoff BE, Felig Y, Gerlitz O, Ben-Hur T, Smith Y, Siegal T (2010) Gliomas display a microRNA expression profile reminiscent of neural precursor cells. Neuro-oncology 12:422–433

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the Natural Science Foundation of Jiangsu Province and Nantong University for the research grants. We also acknowledge the editor and reviewers for their helpful comments on this paper.

Funding

This study was supported by the following grants: Natural Science Foundation of Jiangsu Province (BK20170447), Undergraduate Innovation Training Program of Nantong University (2019141).

Author information

Author notes

  1. Hui He and Juan Liu have contributed equally to this work.

Authors and Affiliations

  1. Department of Human Anatomy, Medical School, Nantong University, Nantong, Jiangsu, People’s Republic of China

    Hui He, Juan Liu, Wen Li, Xiang Yao, Qiqi Ren, Beilei Shen, Cheng Xue, Linqing Zou, Heyan Zhao, Jianbing Qin & Guohua Jin

Authors
  1. Hui He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wen Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiang Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qiqi Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Beilei Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cheng Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Linqing Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Heyan Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jianbing Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Guohua Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guohua Jin.

Ethics declarations

Conflicts of interest

We have no conflicts of interests to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

He, H., Liu, J., Li, W. et al. MiR-210-3p Inhibits Proliferation and Migration of C6 Cells by Targeting Iscu. Neurochem Res 45, 1813–1824 (2020). https://doi.org/10.1007/s11064-020-03043-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-020-03043-w

Keywords

Search

Navigation