Abstract
MYCNOS is an oncogenic lncRNA in liver cancer, but its role in glioblastoma (GBM) is unknown. We predicted that MYCNOS might interact with miR-216b, which targets FOXM1 to perform tumor suppressive roles. This study was performed to analyze the role of MYCNOS in GBM and explore its potential interactions with miR-216b and FOXM1. MYCNOS expression in paired GBM and non-tumor tissues from 62 GBM patients was analyzed by RT-qPCR. The interaction between MYCNOS and miR-216b was predicted by IntaRNA 2.0 and confirmed by dual luciferase activity assay. Overexpression of MYCNOS, miR-216b, and FOXM1 was achieved in GBM cells, followed by performing RT-qPCR and Western blot to explore the relationship among them. CCK-8 assay was performed to explore the role of MYCNOS, miR-216b, and FOXM1 in regulating GBM cell proliferation. MYCNOS was upregulated in GBM tissues compared to the paired non-tumor tissues. MYCNOS is predicted to interact with miR-216b, but overexpression of MYCNOS and miR-216b failed to affect each other’s expression significantly. Dual luciferase activity assay showed that MYCNOS and miR-216b could directly interact with each other. MYCNOS overexpression increased the expression of FOXM1, which is a direct target of miR-216b. Cell proliferation assay showed that MYCNOS and FOXM1 overexpression resulted in an increased proliferation rate of GBM cells, while miR-216b overexpression suppressed cell proliferation. Moreover, MYCNOS overexpression suppressed the role of miR-216b. MYCNOS may regulate FOXM1 expression of by serving as an endogenous sponge of miR-216b axis to promote the proliferation of GBM cells.
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References
Aldape K, Zadeh G, Mansouri S, Reifenberger G, von Deimling A (2015) Glioblastoma: pathology, molecular mechanisms and markers. Acta Neuropathol 129(6):829–848
Alexander BM, Cloughesy TF (2017) Adult glioblastoma. J Clin Oncol 35(21):2402–2409
Brown TJ, Brennan MC, Li M, Church EW, Brandmeir NJ, Rakszawski KL, Patel AS, Rizk EB, Suki D, Sawaya R, Glantz M (2016) Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis. JAMA Oncol 2(11):1460–1469
Cloughesy TF, Cavenee WK, Mischel PS (2014) Glioblastoma: from molecular pathology to targeted treatment. Annu Rev Pathol 9:1–25
Davis ME (2016) Glioblastoma: overview of disease and treatment. Clin J Oncol Nurs 20(5):S2–S8
Huang J, Lyu H, Wang J, Liu B (2015) MicroRNA regulation and therapeutic targeting of survivin in cancer. Am J Cancer Res 5(1):20–31
Li CH, Chen Y (2013) Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol 45(8):1895–1910
Lieberman F (2017) Glioblastoma update: molecular biology, diagnosis, treatment, response assessment, and translational clinical trials. F1000Res 6:1892
Luo L, Zhang Y, He H, Chen C, Zhang B, Cai M (2020) LncRNA FEZF1-AS1 sponges miR-34a to upregulate Notch-1 in Glioblastoma [J]. Cancer Manag Res 12:1827–1833
Mulpur BH, Nabors LB, Thompson RC, Olson JJ, LaRocca R, Thompson Z, Egan KM (2015) Complementary therapy and survival in glioblastoma. Neurooncol Pract 2(3):122–126
O’Brien EM, Selfe JL, Martins AS, Walters ZS, Shipley JM (2018) The long non-coding RNA MYCNOS-01 regulates MYCN protein levels and affects growth of MYCN-amplified rhabdomyosarcoma and neuroblastoma cells. BMC Cancer 18(1):217
Söderberg-Nauclér C, Rahbar A, Stragliotto G (2013) Survival in patients with glioblastoma receiving valganciclovir. N Engl J Med 369(10):985–986
Spizzo R, Almeida MI, Colombatti A, Calin GA (2012) Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene. 31(43):4577–4587
Sun M, Wang X, Tu C, Wang S, Qu J, Xiao S (2017) microRNA-216b inhibits cell proliferation and migration in human melanoma by targeting FOXM1 in vitro and in vivo. Cell Biol Int 41(12):1272–1282
Wiemer EAC (2007) The role of microRNAs in cancer: no small matter. Eur J Cancer 43(10):1529–1544
Yu J, Ou Z, Lei Y, Chen L, Su Q, Zhang K (2020) LncRNA MYCNOS facilitates proliferation and invasion in hepatocellular carcinoma by regulating miR-340. Hum Cell 33(1):148–158
Zhang T, Ma G, Zhang Y, Huo H, Zhao Y (2017) miR-216b inhibits glioma cell migration and invasion through suppression of FoxM1. Oncol Rep 38(3):1751–1759
Zou J, Kuang W, Hu J, Rao H (2017) miR-216b promotes cell growth and enhances chemosensitivity of colorectal cancer by suppressing PDZ-binding kinase. Biochem Biophys Res Commun 488(2):247–252
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Zhi Li designed the study. Ping Zhao carried out experiments and wrote the manuscipt, Zhi Li revised the paper, Ting Li, Youliang Wang, Yong Wang, Qi Gu collected patient specimens and related information. Ping Zhao, Ting Li, Youliang Wang, Yong Wang, Qi Gu contributed to analysing the data. All authors reviewed the results and approved the final version of the manuscript.
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This study was approved by Gansu Provincial Maternity and Childcare Hospital and all the patients or their parents/guardians provided written informed consent.
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Zhao, P., Li, T., Wang, Y. et al. LncRNA MYCNOS promotes glioblastoma cell proliferation by regulating miR-216b/FOXM1 axis. Metab Brain Dis 36, 1185–1189 (2021). https://doi.org/10.1007/s11011-021-00729-0
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DOI: https://doi.org/10.1007/s11011-021-00729-0