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LncRNA GAS5-AS1 inhibits glioma proliferation, migration, and invasion via miR‐106b-5p/TUSC2 axis

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Abstract

Glioma is one of the most common malignant tumors and shows a high metastasis rate and poor prognosis. Abnormal expression of long non-coding RNAs (lncRNAs) contributes to various human tumors including gliomas. This study aimed to investigate the regulatory role of the antisense RNA of growth arrest special 5 (GAS5-AS1), a novel lncRNA, in gliomas. Expression of GAS5-AS1 and microRNA-106b-5p (miR-106b-5p) in glioma tissues and cells was detected by quantitative reverse transcription PCR, northern blotting, or fluorescent in situ hybridization. Cell proliferation, migration, and invasion were analyzed by CCK-8 and Transwell assays. BALB/c nude mice were used to establish a glioma xenograft animal model by subcutaneous injection of U251 cells transfected with small interfering RNA targeting GAS5-AS1. A dual-luciferase reporter assay was conducted to confirm the targeting relationship between GAS5-AS1 and miR-106b-5p. GAS5-AS1 expression was downregulated in glioma tissues and cells, and upregulation of GAS5-AS1 expression inhibited glioma cell proliferation, migration, and invasion. GAS5-AS1 expression was correlated with the glioma tumor grade. In nude mice, upregulation of GAS5-AS1 markedly suppressed glioma tumor growth. GAS5-AS1 overexpression significantly increased the miR-106b-5p level in glioma cells, and GAS5-AS1 expression was negatively related to miR-106b-5p expression in glioma tissues. Overexpression of miR-106b-5p reversed the inhibitory effects of GAS5-AS1 upregulation on glioma cell proliferation and metastasis, while restoration of TUSC2 rescued the proliferation and invasion of glioma cells transfected with miR-106b-5p mimics. In summary, lncRNA GAS5-AS1 inhibited glioma proliferation, migration, and invasion by sponging miR-106b-5p and regulating the expression of TUSC2. Our results suggest GAS5-AS1 as a novel target for the treatment and prognosis prediction of gliomas.

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References

  1. Werner MH, Phuphanich S, Lyman GH. The increasing incidence of malignant gliomas and primary central nervous system lymphoma in the elderly. Cancer. 2015;76:1634–42.

    Article  Google Scholar 

  2. Ohgaki H, Kleihues P. Genetic alterations and signaling pathways in the evolution of gliomas. Cancer Sci. 2010;100:2235–41.

    Article  Google Scholar 

  3. Valadez JG, Sarangi A, Lundberg CJ, Cooper MK (2014) primary orthotopic glioma xenografts recapitulate infiltrative growth and isocitrate dehydrogenase I mutation. J Vis Exp, pp e50865–e65.

  4. Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41.

    Article  CAS  Google Scholar 

  5. Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155–9.

    Article  CAS  Google Scholar 

  6. Zhang F, Zhang L, Zhang C. Long noncoding RNAs and tumorigenesis: genetic associations, molecular mechanisms, and therapeutic strategies. Tumour Biol. 2016;37:163–75.

    Article  Google Scholar 

  7. Matjašič A, Glavač D (2015) Long Noncoding RNAs and Tumorigenesis

  8. Tang J, Jiang R, Deng L, Zhang X, Sun B. Circulation long non-coding RNAs act as biomarkers for predicting tumorigenesis and metastasis in hepatocellular carcinoma. Oncotarget. 2015;6:4505–15.

    PubMed  PubMed Central  Google Scholar 

  9. Ricciuti B, Mencaroni C, Paglialunga L, et al. Long noncoding RNAs: new insights into non-small cell lung cancer biology, diagnosis and therapy. Med Oncol. 2016;33:18.

    Article  Google Scholar 

  10. Li W, Li N, Shi K, Chen Q. Systematic review and meta-analysis of the utility of long non-coding RNA GAS5 as a diagnostic and prognostic cancer biomarker. Oncotarget. 2017;8:66414–25.

    PubMed  PubMed Central  Google Scholar 

  11. Wu Y, Lyu H, Liu H, Shi X, Song Y, Liu B. Downregulation of the long noncoding RNA GAS5-AS1 contributes to tumor metastasis in non-small cell lung cancer. Sci Rep. 2016;6:31093–193.

    Article  CAS  Google Scholar 

  12. Abbastabar M, Sarfi M, Golestani A, Khalili E. lncRNA involvement in hepatocellular carcinoma metastasis and prognosis. EXCLI J. 2018;17:900–13.

    PubMed  PubMed Central  Google Scholar 

  13. Wu W, Lin Z, Zhuang Z, Liang X. Expression profile of mammalian microRNAs in endometrioid adenocarcinoma. Eur J Cancer Prev. 2009;18:50–5.

    Article  CAS  Google Scholar 

  14. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  CAS  Google Scholar 

  15. Yang M, Chen J, Su F, Yu B, Song E. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Mol Cancer. 2011;10:117.

    Article  CAS  Google Scholar 

  16. Yu S, Qin X, Chen T, Zhou L, Feng J. MicroRNA-106b-5p regulates cisplatin chemosensitivity by targeting polycystic kidney disease-2 in non-small-cell lung cancer. Anticancer Drugs. 2017;28:852–60.

    Article  CAS  Google Scholar 

  17. Ni S, Weiwei W, Midie X, et al. miR-106b-5p inhibits the invasion and metastasis of colorectal cancer by targeting CTSA. Oncotargets Therapy. 2018;11:3835–45.

    Article  Google Scholar 

  18. Zheng L, Zhang Y, Liu Y, et al. MiR-106b induces cell radioresistance via the PTEN/PI3K/AKT pathways and p21 in colorectal cancer. J Transl Med. 2015;13:252.

    Article  Google Scholar 

  19. Liu F, Gong J, Huang W, et al. MicroRNA-106b-5p boosts glioma tumorigensis by targeting multiple tumor suppressor genes. Oncogene. 2014;33:4813–22.

    Article  CAS  Google Scholar 

  20. Furnari FB, Fenton T, Bachoo RM, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 2007;21:2683–710.

    Article  CAS  Google Scholar 

  21. Freije AW. Gene expression profiling of gliomas strongly predicts survival. Can Res. 2004;64:6503–10.

    Article  CAS  Google Scholar 

  22. Park JY, Lee JE, Park JB, Yoo H, Lee S-H, Kim JH. Roles of long non-coding rnas on tumorigenesis and glioma development. Brain Tumor Res Treat. 2014;2:1–6.

    Article  Google Scholar 

  23. Ma XL, Zhu WD, Tian LX et al (2017) Long non-coding RNA TUSC7 expression is independently predictive of outcome in glioma. Eur Rev Med Pharmacol Sci, pp 3605–3610.

  24. Wang Y, Jing W, Ma W, Liang C, Chai H, Tu J. Down-regulation of long non-coding RNA GAS5-AS1 and its prognostic and diagnostic significance in hepatocellular carcinoma. Cancer Biomark Sect A Dis Markers. 2018;22:227–36.

    CAS  Google Scholar 

  25. Hu W, Gao A. The role of long non-coding RNAs in hematologic malignancies. Hereditas. 2015;37:1095.

    CAS  PubMed  Google Scholar 

  26. Zhao X, Wang P, Liu J, et al. Gas5 exerts tumor-suppressive functions in human glioma cells by targeting miR-222. Mol Ther. 2015;23:1899–911.

    Article  CAS  Google Scholar 

  27. Nama S, Muhuri M, Di Pascale F, et al. MicroRNA-138 is a prognostic biomarker for triple-negative breast cancer and promotes tumorigenesis via TUSC2 repression. Sci Rep. 2019;9:12718.

    Article  Google Scholar 

  28. Xie HH, Huan WT, Han JQ, Ren WR, Yang LH. MicroRNA-663 facilitates the growth, migration and invasion of ovarian cancer cell by inhibiting TUSC2. Biol Res. 2019;52:18.

    Article  Google Scholar 

  29. Xin J, Zhang XK, Xin DY, et al. FUS1 acts as a tumor-suppressor gene by upregulating miR-197 in human glioblastoma. Oncol Rep. 2015;34:868–76.

    Article  CAS  Google Scholar 

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Funding

This work was supported by National Natural Science Foundation of China (81302181) and the Key Research and Development Program of Jiangsu Province (No. BE2019652).

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Author notes

  1. Wu Huang, Yu Shi and Bin Han contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Nanjing Medical University Affiliated Changzhou No. 2 People’s Hospital, Changzhou, 213003, Jiangsu, China

    Wu Huang, Bin Han, Qilong Wang & Fang Liu

  2. Department of Neurology, Xuzhou Third People’s Hospital, Xuzhou, Jiangsu, China

    Yu Shi

  3. Department of Neurosurgery, JinTan People’s Hospital, Changzhou, Jiangsu, China

    Bin Zhang

  4. Central Laboratory, Nanjing Medical University Affiliated Changzhou No. 2 People’s Hospital, Changzhou, Jiangsu, China

    Chunjian Qi

Authors
  1. Wu Huang
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  2. Yu Shi
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  3. Bin Han
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  4. Qilong Wang
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  5. Bin Zhang
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  6. Chunjian Qi
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  7. Fang Liu
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Contributions

FL conceived and designed research; WH and YS performed experiments; BH analyzed data; QW interpreted results of experiments; BZ prepared figures; CQ drafted, edited, and revised manuscript.

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Correspondence to Fang Liu.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving animals were in accordance with the ethical standards of Nanjing University. All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Changzhou No. 2 People’s Hospital, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Huang, W., Shi, Y., Han, B. et al. LncRNA GAS5-AS1 inhibits glioma proliferation, migration, and invasion via miR‐106b-5p/TUSC2 axis. Human Cell 33, 416–426 (2020). https://doi.org/10.1007/s13577-020-00331-z

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  • DOI: https://doi.org/10.1007/s13577-020-00331-z

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