Abstract
Dysregulated circular RNAs (circRNAs) have been confirmed to partake in the modulation of the glioma progression. Here, we intended to explore the role of circBRAF in glioma and the possible action mechanism. The expression levels of circBRAF, microRNA (miR)-1290 and F-box and WD repeat domain containing 7 (FBXW7) were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot. Cell viability was assessed by 3-(4, 5)-dimethylthiazole-2-y1)-2, 5-biphenyl tetrazolium bromide (MTT) assay. Cell cycle distribution was determined by flow cytometry. Cell migration and invasion were evaluated through Trans-well assay. Related protein levels were detected by western blot. Targeted relation among circBRAF, miR-1290 and FBXW7 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP) and pull-down assays. Xenograft model was constructed to explore the function of circBRAF in vivo. Expression of circBRAF and FBXW7 was decreased in glioma tissues and cells. Upregulation of circBRAF inhibited glioma cell proliferation and metastasis in vitro. MiR-1290 was upregulated in glioma, which was sponged by circBRAF. Besides, circBRAF elevated FBXW7 expression by targeting miR-1290. Introduction of miR-1290 or FBXW7 knockdown could counteract the inhibitory effects of circBRAF upregulation on the malignant phenotypes of glioma cells. Overexpression of circBRAF repressed the tumor growth in vivo. Upregulation of circBRAF suppressed glioma evolvement in vitro and in vivo by regulating miR-1290/FBXW7 axis, broadening the cognition of glioma progression.
Similar content being viewed by others
References
McComb RD, Burger PC (1985) Pathologic analysis of primary brain tumors. Neurol Clin 3:711–728
Lapointe S, Perry A, Butowski NA (2018) Primary brain tumours in adults. Lancet 392:432–446
Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C, Barnholtz-Sloan J (2014) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007–2011. Neuro Oncol 16(Suppl 4):iv1–iv63
Chen H, Chen G, Li G, Zhang S, Chen H, Chen Y, Duggan D, Hu Z, Chen J, Zhao Y, Zhao Y, Huang H, Zheng SL, Trent JM, Yu L, Jiang D, Mo Z, Wang H, Mou Y, Jiang T, Mao Y, Xu J, Lu D (2019) Two novel genetic variants in the STK38L and RAB27A genes are associated with glioma susceptibility. Int J Cancer 145:2372–2382
Tanaka S, Louis DN, Curry WT, Batchelor TT, Dietrich J (2013) Diagnostic and therapeutic avenues for glioblastoma: no longer a dead end? Nat Rev Clin Oncol 10:14–26
Little MP, de Vathaire F, Shamsaldin A, Oberlin O, Campbell S, Grimaud E, Chavaudra J, Haylock RG, Muirhead CR (1998) Risks of brain tumour following treatment for cancer in childhood: modification by genetic factors, radiotherapy and chemotherapy. Int J Cancer 78:269–275
Mazurek M, Litak J, Kamieniak P, Kulesza B, Jonak K, Baj J, Grochowski C (2020) Metformin as potential therapy for high-grade glioma. Cancers (Basel) 12(1):210
Meng S, Zhou H, Feng Z, Xu Z, Tang Y, Li P, Wu M (2017) CircRNA: functions and properties of a novel potential biomarker for cancer. Mol Cancer 16:94
Hao Z, Hu S, Liu Z, Song W, Zhao Y, Li M (2019) Circular RNAs: functions and prospects in glioma. J Mol Neurosci 67:72–81
Yang M, Li G, Fan L, Zhang G, Xu J, Zhang J (2019) Circular RNA circ_0034642 elevates BATF3 expression and promotes cell proliferation and invasion through miR-1205 in glioma. Biochem Biophys Res Commun 508:980–985
Li G, Yang H, Han K, Zhu D, Lun P, Zhao Y (2018) A novel circular RNA, hsa_circ_0046701, promotes carcinogenesis by increasing the expression of miR-142-3p target ITGB8 in glioma. Biochem Biophys Res Commun 498:254–261
Li F, Ma K, Sun M, Shi S (2018) Identification of the tumor-suppressive function of circular RNA ITCH in glioma cells through sponging miR-214 and promoting linear ITCH expression. Am J Transl Res 10:1373–1386
Zhu J, Ye J, Zhang L, Xia L, Hu H, Jiang H, Wan Z, Sheng F, Ma Y, Li W, Qian J, Luo C (2017) Differential expression of circular RNAs in glioblastoma multiforme and its correlation with prognosis. Transl Oncol 10:271–279
Lynam-Lennon N, Maher SG, Reynolds JV (2009) The roles of microRNA in cancer and apoptosis. Biol Rev Camb Philos Soc 84:55–71
Mazurek M, Litak J, Kamieniak P, Osuchowska I, Maciejewski R, Roliński J, Grajkowska W, Grochowski C (2020) Micro RNA molecules as modulators of treatment resistance, immune checkpoints controllers and sensitive biomarkers in glioblastoma multiforme. Int J Mol Sci 21(4):1507
Zhou Q, Liu J, Quan J, Liu W, Tan H, Li W (2018) MicroRNAs as potential biomarkers for the diagnosis of glioma: a systematic review and meta-analysis. Cancer Sci 109:2651–2659
Dong Q, Yuan G, Liu M, Xie Q, Hu J, Wang M, Liu S, Ma X, Pan Y (2019) Downregulation of microRNA-374a predicts poor prognosis in human glioma. Exp Ther Med 17:2077–2084
Wang LQ, Sun W, Wang Y, Li D, Hu AM (2019) Downregulation of plasma miR-124 expression is a predictive biomarker for prognosis of glioma. Eur Rev Med Pharmacol Sci 23:271–276
Yan L, Cai K, Sun K, Gui J, Liang J (2018) MiR-1290 promotes proliferation, migration, and invasion of glioma cells by targeting LHX6. J Cell Physiol 233:6621–6629
Yeh CH, Bellon M, Nicot C (2018) FBXW7: a critical tumor suppressor of human cancers. Mol Cancer 17:115
Peng G, Yang C, Liu Y, Shen C (2019) miR-25-3p promotes glioma cell proliferation and migration by targeting FBXW7 and DKK3. Exp Ther Med 18:769–778
Wang D, Yang S, Wang H, Wang J, Zhang Q, Zhou S, He Y, Zhang H, Deng F, Xu H, Zhong S, Fu L, Tang J (2018) The progress of circular RNAs in various tumors. Am J Transl Res 10:1571–1582
Yuan Y, Jiaoming L, Xiang W, Yanhui L, Shu J, Maling G, Qing M (2018) Analyzing the interactions of mRNAs, miRNAs, lncRNAs and circRNAs to predict competing endogenous RNA networks in glioblastoma. J Neurooncol 137:493–502
Thomson DW, Dinger ME (2016) Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet 17:272–283
Sun Y, Ju XL, Li D, Zhou PP, Li X, Luo RH (2019) miR-1290 promotes proliferation and suppresses apoptosis in acute myeloid leukemia by targeting FOXG1/SOCS3. J Biol Regul Homeost Agents 33:1703–1713
Qin WJ, Wang WP, Wang XB, Zhang XT, Du JD (2019) MiR-1290 targets CCNG2 to promote the metastasis of oral squamous cell carcinoma. Eur Rev Med Pharmacol Sci 23:10332–10342
Jin JJ, Liu YH, Si JM, Ni R, Wang J (2018) Overexpression of miR-1290 contributes to cell proliferation and invasion of non small cell lung cancer by targeting interferon regulatory factor 2. Int J Biochem Cell Biol 95:113–120
Liu X, Ma J, Xu F, Li L (2018) TINCR suppresses proliferation and invasion through regulating miR-544a/FBXW7 axis in lung cancer. Biomed Pharmacother 99:9–17
Xia W, Zhou J, Luo H, Liu Y, Peng C, Zheng W, Ma W (2017) MicroRNA-32 promotes cell proliferation, migration and suppresses apoptosis in breast cancer cells by targeting FBXW7. Cancer Cell Int 17:14
Liu S, Liu H, Deng M, Wang H (2020) MiR-182 promotes glioma progression by targeting FBXW7. J Neurol Sci 411:116689
Funding
None.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no financial conflicts of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Zhang, J., Chen, Z., Liu, X. et al. Gain of circBRAF Represses Glioma Progression by Regulating miR-1290/FBXW7 Axis. Neurochem Res 46, 1203–1213 (2021). https://doi.org/10.1007/s11064-021-03259-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-021-03259-4