miR-22 inhibits the proliferation, motility, and invasion of human glioblastoma cells by directly targeting SIRT1 (original) (raw)

Abstract

Recently, microRNAs (miRNAs), a kind of small and non-coding RNA, can target the downstream molecules. Increasing evidence demonstrates that miRNAs meditate the onset and progression of a variety of tumors. In the present study, we carried out gene transfection, western blot, and reverse transcription PCR (RT-PCR) to explore the role of miR-22 in glioblastoma tissues and cell lines. Here, we verified that the expression of miR-22 was downregulated in glioblastoma tissues and cells rather than matched non-tumor tissues and normal human astrocyte (NHA) cells (p < 0.001). By contrast, SIRT1 messenger RNA (mRNA) and protein were upregulated in glioblastoma tissues and cells (p < 0.001). In vitro miR-22 mimics interfered with cell proliferation, migration, and invasion of U87 and U251 cells. Mechanically, the 3′-untranslated regions (3′-UTRs) of SIRT1 were a direct target of miR-22, leading to the decreased expression of SIRT1 protein in U87 and U251 cells. Meanwhile, miR-22 mimics also inhibited the expression of epidermal growth factor receptor (EGFR) and matrix metallopeptidase 9 (MMP9). In conclusion, miR-22 inhibited cell proliferation, migration, and invasion via targeting the 3′-UTR of SIRT1 in the progression of glioblastoma and miR-22-SIRT1 pathway can be recommended as a potential target for treatment of glioblastoma.

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References

  1. Jemal A, Siegel R, Xu J. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.
    Article PubMed Google Scholar
  2. Liao A, Shi R, Jiang Y, Tian S, Li P, Song F, et al. SDF-1/CXCR4 axis regulates cell cycle progression and epithelial-mesenchymal transition via up-regulation of survivin in glioblastoma. Mol Neurobiol. 2014 Nov 25.
  3. Lv Q, Zhang J, Yi Y, Huang Y, Wang Y, Wang Y, et al. Proliferating cell nuclear antigen has an association with prognosis and risks factors of cancer patients: a systematic review. Mol Neurobiol. 2015.
  4. Lv B, Yang X, Lv S, Wang L, Fan K, Shi R, et al. CXCR4 signaling induced epithelial-mesenchymal transition by PI3K/AKT and ERK pathways in glioblastoma. Mol Neurobiol. 2015;52(3):1263–8.
    Article CAS PubMed Google Scholar
  5. Altieri R, Fontanella M, Agnoletti A, Panciani PP, Spena G, Crobeddu E, et al. Role of nitric oxide in glioblastoma therapy: another step to resolve the terrible puzzle? Transl Med UniSa. 2014;12:54–9.
    PubMed PubMed Central Google Scholar
  6. De Paepe A, Vandeneede N, Strens D, Specenier P. The economics of the treatment and follow-up of patients with glioblastoma. Value Health. 2015;18(7):A448.
    Article Google Scholar
  7. Kagiya T. MicroRNAs and osteolytic bone metastasis: the roles of microRNAs in tumor-induced osteoclast differentiation. J Clin Med. 2015;4(9):1741–52.
    Article PubMed PubMed Central Google Scholar
  8. Sanei M, Chen X. Mechanisms of microRNA turnover. Curr Opin Plant Biol. 2015;27:199–206.
    Article CAS PubMed PubMed Central Google Scholar
  9. Luna-Aguirre CM, de la Luz M-FM, 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.
    Article CAS PubMed Google Scholar
  10. Sampson VB, Yoo S, Kumar A, Vetter NS, Kolb EA. MicroRNAs and potential targets in osteosarcoma: review. Front Pediatr. 2015;3:69.
    Article PubMed PubMed Central Google Scholar
  11. Kanda M, Kodera Y. Recent advances in the molecular diagnostics of gastric cancer. World J Gastroenterol. 2015;21(34):9838–52.
    Article CAS PubMed PubMed Central Google Scholar
  12. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433(7027):769–73.
    Article CAS PubMed Google Scholar
  13. Lu W, You R, Yuan X, Yang T, Samuel EL, Marcano DC, et al. The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote TH17 cell-dependent emphysema. Nat Immunol. 2015;16(11):1185–94.
    Article CAS PubMed PubMed Central Google Scholar
  14. Yang Q, Jiang W, Zhuang C, Geng Z, Hou C, Huang D, et al. MicroRNA-22 downregulation of galectin-9 influences lymphocyte apoptosis and tumor cell proliferation in liver cancer. Oncol Rep. 2015;34(4):1771–8.
    CAS PubMed Google Scholar
  15. Zhou Y, Zhou Z, Zhang W, Hu X, Wei H, Peng J, et al. SIRT1 inhibits adipogenesis and promotes myogenic differentiation in C3H10T1/2 pluripotent cells by regulating Wnt signaling. Cell Biosci. 2015;5:61.
    Article PubMed PubMed Central Google Scholar
  16. Maiese K. MicroRNAs and SIRT1: a strategy for stem cell renewal and clinical development? J Transl Sci. 2015;1(3):55–7.
    PubMed PubMed Central Google Scholar
  17. Shuang T, Wang M, Zhou Y, Shi C. Over-expression of Sirt1 contributes to chemoresistance and indicates poor prognosis in serous epithelial ovarian cancer (EOC). Med Oncol. 2015;32(12):260.
    Article PubMed Google Scholar
  18. Xiong J, Yu D, Wei N, Fu H, Cai T, Huang Y, et al. An estrogen receptor alpha suppressor, microRNA-22, is downregulated in estrogen receptor alpha-positive human breast cancer cell lines and clinical samples. FEBS J. 2010;277:1684–94.
    Article CAS PubMed Google Scholar
  19. García I, Vizoso F, Andicoechea A, Fernandez P, Suarez C, García-Muñz JL, et al. C-erbB-2 oncoprotein content in gastric cancer and in adjacent mucosa. Int J Biol Markers. 2000;15(3):231–4.
    PubMed Google Scholar
  20. Dan L, Jian D, Na L, Xiaozhong W. Crosstalk between EGFR and integrin affects invasion and proliferation of gastric cancer cell line, SGC7901. Onco Targets Ther. 2012;5:271–7.
    PubMed PubMed Central Google Scholar
  21. Chen W, Zhong X, Wei Y, Liu Y, Yi Q, Zhang G, et al. TGF-β regulates survivin to affect cell cycle and the expression of EGFR and MMP9 in glioblastoma. Mol Neurobiol. 2015.
  22. Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010;141(1):52–67.
    Article CAS PubMed PubMed Central Google Scholar
  23. Yang X, Lv S, Liu Y, Li D, Shi R, Tang Z, et al. The clinical utility of matrix metalloproteinase 9 in evaluating pathological grade and prognosis of glioma patients: a meta-analysis. Mol Neurobiol. 2015;52(1):38–44.
    Article CAS PubMed Google Scholar
  24. Kumar B, Koul S, Petersen J, Khandrika L, Hwa JS, Meacham RB, et al. p38 mitogen-activated protein kinase-driven MAPKAPK2 regulates invasion of bladder cancer by modulation of MMP-2 and MMP-9 activity. Cancer Res. 2010;70(2):832–41.
    Article CAS PubMed Google Scholar
  25. Yao C, Li P, Song H, Song F, Qu Y, Ma X, et al. CXCL12/CXCR4 axis upregulates twist to induce EMT in human glioblastoma. Mol Neurobiol. 2015.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Project No. 81502163 and 31370810). We greatly thank Bo Hong in Department of Neurosurgery, Changhai Hospital, Second Military Medical University (Shanghai, 200433, P.R. China) for valuable suggestions and his fund.

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Authors and Affiliations

  1. Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, Jiangsu, 215021, China
    Hanchun Chen, Xifeng Fei, Likui Shen & Dongyi Jiang
  2. Department of Laboratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China
    Qiong Lu
  3. Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China
    Dongwei Dai

Authors

  1. Hanchun Chen
  2. Qiong Lu
  3. Xifeng Fei
  4. Likui Shen
  5. Dongyi Jiang
  6. Dongwei Dai

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Correspondence toDongwei Dai.

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Hanchun Chen and Qiong Lu contributed equally to this work.

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Chen, H., Lu, Q., Fei, X. et al. miR-22 inhibits the proliferation, motility, and invasion of human glioblastoma cells by directly targeting SIRT1.Tumor Biol. 37, 6761–6768 (2016). https://doi.org/10.1007/s13277-015-4575-8

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