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Downregulation of hsa_circ_0000936 sensitizes resistant glioma cells to temozolomide by sponging miR-1294

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Abstract

Glioma is one of the most aggressive forms of brain tumor and is hallmarked by high rate of mortality, metastasis and drug resistance. Herein, we explore the role of circular RNA (circRNA) hsa_circ_0000936 in the resistance of glioma cells to temozolomide (TMZ). In this study, Relative changes in gene expression levels were compared using qRT-PCR. The role of hsa_circ_0000936 was characterized by cell count kit -8 assay and flow cytometry. Luciferase reporter assay was carried out for target validation.We found that hsa_circ_0000936 was upregulated in glioma tissues as compared to their adjacent normal tissues. Increased expression of hsa_circ_0000936 was found in the glioma tissues of patients showing resistance to TMZ compared with that of patients showing sensitivity to TMZ. The upregulation of hsa_circ_0000936 was also confirmed in TMZ-resistant glioma cells. miR-1294 was downregulated in TMZ-resistant glioma cells and identified as a direct target of hsa_circ_0000936. Downregulation of hsa_circ_0000936 increased the sensitivity of TMZ-resistant glioma cells towards TMZ. Moreover, restoration of miR-1294 could abrogate the promoting effect of hsa_circ_0000936 on TMZ resistance in TMZ-resistant glioma cells. In conclusion, downregulation of hsa_circ_0000936 sensitizes TMZ-resistant glioma cells to TMZ by sponging miR-1294, suggesting that hsa_circ_0000936 may be a potential target for overcoming the resistance of glioma cells to TMZ.

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References

  • Arnaiz E, Sole C, Manterola L, Iparraguirre L, Otaegui D and Lawrie CH 2018 CircRNAs and cancer: Biomarkers and master regulators. Semin. Cancer Biol. 58 90–99

    Article  Google Scholar 

  • Barrett SP and Salzman J 2016 Circular RNAs: analysis, expression and potential functions. Development 143 1838–1847

    Article  CAS  Google Scholar 

  • Brada M, et al. 2003 Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas. Ann. Oncol. 14 1715–1721

    Article  CAS  Google Scholar 

  • Chen H, Liu L, Li X, Shi Y and Liu N 2018 MicroRNA-1294 inhibits the proliferation and enhances the chemosensitivity of glioma to temozolomide via the direct targeting of TPX2. Am. J. Cancer Res. 8 291–301

    CAS  PubMed  PubMed Central  Google Scholar 

  • Conn SJ, Pillman KA, Toubia J, Conn VM, Salmanidis M, Phillips CA, Roslan S, Schreiber AW, Gregory PA and Goodall GJ 2015 The RNA binding protein quaking regulates formation of circRNAs. Cell 160 1125–1134

    Article  CAS  Google Scholar 

  • Gao D, Zhang X, Liu B, Meng D, Fang K, Guo Z and Li L 2017 Screening circular RNA related to chemotherapeutic resistance in breast cancer. Epigenomics 9 1175–1188

    Article  CAS  Google Scholar 

  • Geng Y, Jiang J and Wu C 2018 Function and clinical significance of circRNAs in solid tumors. J. Hematol. Oncol. 11 98

    Article  Google Scholar 

  • Guo TY, Xu HY, Chen WJ, Wu MX and Dai X 2018 Downregulation of miR-1294 associates with prognosis and tumor progression in epithelial ovarian cancer. Eur. Rev. Med. Pharmacol. Sci. 22 7646–7652

    PubMed  Google Scholar 

  • Hao Z, Hu S, Liu Z, Song W, Zhao Y and Li M 2019 Circular RNAs: Functions and prospects in glioma. J. Mol. Neurosci. 67 72–81

    Article  CAS  Google Scholar 

  • He Q, et al. 2018 circ-SHKBP1 Regulates the Angiogenesis of U87 glioma-exposed endothelial cells through miR-544a/FOXP1 and miR-379/FOXP2 pathways. Mol. Ther. Nucleic Acids 10 331–348

    Article  CAS  Google Scholar 

  • Hombach-Klonisch S, et al. 2018 Glioblastoma and chemoresistance to alkylating agents: Involvement of apoptosis, autophagy, and unfolded protein response. Pharmacol. Ther. 184 13–41

    Article  CAS  Google Scholar 

  • Huang X, et al. 2019 Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression. Mol. Cancer. 18 71

    Article  Google Scholar 

  • Kun-Peng Z, Xiao-Long M and Chun-Lin Z 2018 Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1. Int. J. Biol. Sci. 14 321–330

    Article  Google Scholar 

  • Lei B, Huang Y, Zhou Z, Zhao Y, Thapa AJ, Li W, Cai W and Deng Y 2019 Circular RNA hsa_circ_0076248 promotes oncogenesis of glioma by sponging miR-181a to modulate SIRT1 expression. J. Cell Biochem. 120 6698–6708

    Article  CAS  Google Scholar 

  • Li X, Yang L and Chen LL 2018 The biogenesis, functions, and challenges of circular RNAs. Mol. Cell. 71 428–442

    Article  CAS  Google Scholar 

  • Liu K, Li L, Rusidanmu A, Wang Y and Lv X 2015 Down-regulation of MiR-1294 is related to dismal prognosis of patients with esophageal squamous cell carcinoma through elevating C-MYC expression. Cell Physiol. Biochem. 36 100–110

    Article  Google Scholar 

  • Liu Y, Dong Y, Zhao L, Su L and Luo J 2018 Circular RNAMTO1 suppresses breast cancer cell viability and reverses monastrol resistance through regulating the TRAF4/Eg5 axis. Int. J. Oncol. 53 1752–1762

    CAS  PubMed  Google Scholar 

  • Margison GP, Santibanez Koref MF and Povey AC 2002 Mechanisms of carcinogenicity/chemotherapy by O6-methylguanine. Mutagenesis 17 483–487

    Article  CAS  Google Scholar 

  • Memczak S, et al. 2013 Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495 333–338

    Article  CAS  Google Scholar 

  • Mercatelli N, Galardi S and Ciafre SA 2017 MicroRNAs as Multifaceted Players in Glioblastoma Multiforme. Int. Rev. Cell Mol. Biol. 333 269–323

    Article  CAS  Google Scholar 

  • Ostrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C and Barnholtz-Sloan JS 2016 CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro. Oncol. 18 v1–v75

    Article  Google Scholar 

  • Rupaimoole R, Calin GA, Lopez-Berestein G and Sood AK 2016 miRNA Deregulation in cancer cells and the tumor microenvironment. Cancer Discov. 6 235–246

    Article  CAS  Google Scholar 

  • Salmena L, Poliseno L, Tay Y, Kats L and Pandolfi PP 2011 A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146 353–358

    Article  CAS  Google Scholar 

  • Shi YX, Ye BL, Hu BR and Ruan XJ 2018 Expression of miR-1294 is downregulated and predicts a poor prognosis in gastric cancer. Eur. Rev. Med. Pharmacol. Sci. 22 5525–5530

    PubMed  Google Scholar 

  • Sun W, Julie Li YS, Huang HD, Shyy JY and Chien S 2010 microRNA: a master regulator of cellular processes for bioengineering systems. Annu. Rev. Biomed. Eng. 12 1–27

    Article  CAS  Google Scholar 

  • van Thuijl HF, et al. 2015 Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment. Acta Neuropathol. 129 597–607

    Article  Google Scholar 

  • Wang R, Zhang S, Chen X, Li N, Li J, Jia R, Pan Y and Liang H 2018a CircNT5E acts as a sponge of miR-422a to promote glioblastoma tumorigenesis. Cancer Res. 78 4812–4825

    Article  CAS  Google Scholar 

  • Wang Z, Yan J, Zou T and Gao H 2018b MicroRNA-1294 inhibited oral squamous cell carcinoma growth by targeting c-Myc. Oncol. Lett. 16 2243–2250

    PubMed  PubMed Central  Google Scholar 

  • Wu Y, et al. 2019 Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression. Mol. Cancer 18 73

    Article  Google Scholar 

  • Xu C, Yu Y and Ding F 2018 Microarray analysis of circular RNA expression profiles associated with gemcitabine resistance in pancreatic cancer cells. Oncol. Rep. 40 395–404

    CAS  PubMed  Google Scholar 

  • Zhang Y, Huang S, Guo Y and Li L 2018a MiR-1294 confers cisplatin resistance in ovarian cancer cells by targeting IGF1R. Biomed. Pharmacother. 106 1357–1363

    Article  CAS  Google Scholar 

  • Zhang ZF, Li GR, Cao CN, Xu Q, Wang GD and Jiang XF 2018b MicroRNA-1294 targets HOXA9 and has a tumor suppressive role in osteosarcoma. Eur. Rev. Med. Pharmacol. Sci. 22 8582–8588

    PubMed  Google Scholar 

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Acknowledgements

This study was funded by the National Natural Science Foundation of China (No. 81873186).

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Authors and Affiliations

  1. First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China

    Lin Hua, Lifa Huang & Haoke Feng

  2. Department of Neurosurgery, Zhejiang Provincial Hospital of Traditional Chinese Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China

    Lifa Huang & Xin Zhang

Authors
  1. Lin Hua
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  2. Lifa Huang
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  3. Xin Zhang
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  4. Haoke Feng
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Corresponding author

Correspondence to Lifa Huang.

Additional information

Communicated by Sorab Dalal.

Corresponding editor: Sorab Dalal

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Hua, L., Huang, L., Zhang, X. et al. Downregulation of hsa_circ_0000936 sensitizes resistant glioma cells to temozolomide by sponging miR-1294. J Biosci 45, 101 (2020). https://doi.org/10.1007/s12038-020-00072-z

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  • DOI: https://doi.org/10.1007/s12038-020-00072-z

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