Abstract
To explore the functions of circRNA cyclin B1 (circCCNB1) in glioma and its possible mechanisms. The expression of circCCNB1, eukaryotic translation initiation factor 4A3 (EIF4A3), cyclin D1 (CCND1) and miR-516b-5p was determined by qRT-PCR, western blot or immunohistochemistry (IHC) assay. The feature of circCCNB1 was analyzed by Actinomycin D (ActD), RNase R and subcellular fraction assays. The molecule relationships were analyzed by RIP, dual-luciferase reporter and RNA pull-down assays. CCK-8, EdU and colony formation assays were performed to analyze cell proliferation. Flow cytometry analysis was executed to estimate the cell cycle. Murine xenograft model assay was used for the role of circCCNB1 in vivo. CircCCNB1 was overexpressed in glioma tissues and cells. EIF4A3 positively regulated circCCNB1 expression. CircCCNB1 knockdown repressed glioma cell proliferation and cell cycle process in vitro and blocked tumor growth in vivo. CircCCNB1 knockdown reduced CCND1 expression in glioma cells and CCND1 overexpression bated the effect of circCCNB1 knockdown on glioma cell growth. CircCCNB1 interacted with HuR to elevate CCND1 expression. miR-516b-5p could interact with circCCNB1 and CCND1. CircCCNB1 regulated glioma cell progression and CCND1 expression by miR-516b-5p and HuR. CircCCNB1 aggravated glioma cell growth by elevating CCND1 through targeting miR-516b-5p and HuR.
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References
Abdelmohsen K, Panda AC, Munk R, Grammatikakis I, Dudekula DB, De S et al (2017) Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1. RNA Biol 14(3):361–369
Bush NA, Chang SM, Berger MS (2017) Current and future strategies for treatment of glioma. Neurosurg Rev 40(1):1–14
Cahill D, Turcan S (2018) Origin of Gliomas. Semin Neurol 38(1):5–10
Chan CC, Dostie J, Diem MD, Feng W, Mann M, Rappsilber J et al (2004) eIF4A3 is a novel component of the exon junction complex. RNA 10(2):200–209
Chen LL, Yang L (2015) Regulation of circRNA biogenesis. RNA Biol 12(4):381–388
Conn SJ, Pillman KA, Toubia J, Conn VM, Salmanidis M, Phillips CA et al (2015) The RNA binding protein quaking regulates formation of circRNAs. Cell 160(6):1125–1134
Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A et al (2007) Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 21(21):2683–2710
Garcia-Maurino SM, Rivero-Rodriguez F, Velazquez-Cruz A, Hernandez-Vellisca M, Diaz-Quintana A, De la Rosa MA et al (2017) RNA Binding Protein Regulation and Cross-Talk in the Control of AU-rich mRNA Fate. Front Mol Biosci 4:71
Ghosh U, Adhya S (2018) Posttranscriptional regulation of cyclin D1 by ARE-binding proteins AUF1 and HuR in cycling myoblasts. J Biosci 43(4):685–691
Han C, Wang S, Wang H, Zhang J (2020) Knockdown of circ-TTBK2 inhibits glioma progression by regulating miR-1283 and CHD1. Cancer Manag Res 12:10055–10065
Heinonen M, Fagerholm R, Aaltonen K, Kilpivaara O, Aittomaki K, Blomqvist C et al (2007) Prognostic role of HuR in hereditary breast cancer. Clin Cancer Res 13(23):6959–6963
Huang Y, Jiang L, Wei G (2021) Circ_0006168 promotes the migration, invasion and proliferation of esophageal squamous cell carcinoma cells via miR-516b-5p-dependent regulation of XBP1. Onco Targets Ther 14:2475–2488
Jansson MD, Lund AH (2012) MicroRNA and cancer. Mol Oncol 6(6):590–610
Liu B, Yang G, Wang X, Liu J, Lu Z, Wang Q et al (2020a) CircBACH1 (hsa_circ_0061395) promotes hepatocellular carcinoma growth by regulating p27 repression via HuR. J Cell Physiol 235(10):6929–6941
Liu J, Hou K, Ji H, Mi S, Yu G, Hu S et al (2020b) Overexpression of circular RNA circ-CDC45 facilitates glioma cell progression by sponging miR-516b and miR-527 and predicts an adverse prognosis. J Cell Biochem 121(1):690–697
Liu NZ, Li T, Liu CM, Liu FR, Wang YX (2020c) Hsa_circ_0000337 promotes proliferation, migration and invasion in glioma by competitively binding miRNA-942-5p and thus upregulates MAT2A. Eur Rev Med Pharmacol Sci 24(23):12251–12257
Liu H, Lan T, Li H, Xu L, Chen X, Liao H et al (2021) Circular RNA circDLC1 inhibits MMP1-mediated liver cancer progression via interaction with HuR. Theranostics 11(3):1396–1411
Lopez de Silanes I, Fan J, Yang X, Zonderman AB, Potapova O, Pizer ES et al (2003) Role of the RNA-binding protein HuR in colon carcinogenesis. Oncogene 22(46):7146–7154
Ng WL, Mohd Mohidin TB, Shukla K (2018) Functional role of circular RNAs in cancer development and progression. RNA Biol 15(8):995–1005
Ostrom QT, Gittleman H, Stetson L, Virk SM, Barnholtz-Sloan JS (2015) Epidemiology of gliomas. Cancer Treat Res 163:1–14
Patop IL, Wust S, Kadener S (2019) Past, present, and future of circRNAs. EMBO J 38(16):e100836
Shen H, Xu L, You C, Tang H, Wu H, Zhang Y et al (2021) miR-665 is downregulated in glioma and inhibits tumor cell proliferation, migration and invasion by targeting high mobility group box 1. Oncol Lett 21(2):156
Sotoudeh H, Shafaat O, Bernstock JD, Brooks MD, Elsayed GA, Chen JA et al (2019) Artificial Intelligence in the Management of Glioma: Era of Personalized Medicine. Front Oncol 9:768
Wang Y, Mo Y, Gong Z, Yang X, Yang M, Zhang S et al (2017) Circular RNAs in human cancer. Mol Cancer 16(1):25
Wang L, Shang X, Feng Q (2019) LncRNA TATDN1 contributes to the cisplatin resistance of non-small cell lung cancer through TATDN1/miR-451/TRIM66 axis. Cancer Biol Ther 20(3):261–271
Wang T, Zhang Y, Cui B, Wang M, Li Y, Gao K (2020a) miR-4530 inhibits the malignant biological behaviors of human glioma cells by directly targeting RTEL1. Acta Biochim Biophys Sin (Shanghai) 52(12):1394–1403
Wang X, Feng H, Dong W, Wang F, Zhang G, Wu J (2020b) Hsa_circ_0008225 inhibits tumorigenesis of glioma via sponging miR-890 and promoting ZMYND11 expression. J Pharmacol Sci 143(2):74–82
Wang X, Zhu Y (2021) Circ_0000020 elevates the expression of PIK3CA and facilitates the malignant phenotypes of glioma cells via targeting miR-142-5p. Cancer Cell Int 21(1):79
Xie P, Han Q, Liu D, Yao D, Lu X, Wang Z et al (2020) miR-525-5p modulates proliferation and epithelial-mesenchymal transition of glioma by targeting stat-1. Onco Targets Ther 13:9957–9966
Xie Y, Liu X, Hu T, Wang W (2020) miR-302e suppresses glioma progression by targeting VEGFA. Cancer Manag Res 12:10965–10974
Zang Y, Li J, Wan B, Tai Y (2020) circRNA circ-CCND1 promotes the proliferation of laryngeal squamous cell carcinoma through elevating CCND1 expression via interacting with HuR and miR-646. J Cell Mol Med 24(4):2423–2433
Zuo CY, Qian W, Huang CJ, Lu J (2019) Circular RNA circ-SMAD7 promoted glioma cell proliferation and metastasis by upregulating PCNA. Eur Rev Med Pharmacol Sci 23(22):10035–10041
Zhou H, Zhang Y, Lai Y, Xu C, Cheng Y (2020) Circ_101064 regulates the proliferation, invasion and migration of glioma cells through miR-154-5p/ PIWIL1 axis. Biochem Biophys Res Commun 523(3):608–614
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Faming Zhou designed and supervised the study. Xiaoli Li and Chengmou Wang conducted the experiments and drafted the manuscript. Guanghui Chen and Wenqin Zou collected and analyzed the data. Yanqing Deng contributed the methodology, operated the software and edited the manuscript.
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Li, X., Wang, C., Chen, G. et al. EIF4A3-induced circCCNB1 (hsa_circ_0001495) promotes glioma progression by elevating CCND1 through interacting miR-516b-5p and HuR. Metab Brain Dis 37, 819–833 (2022). https://doi.org/10.1007/s11011-021-00899-x
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DOI: https://doi.org/10.1007/s11011-021-00899-x