Abstract
Hsa_circRNA_0008344 (circ_0008344) is a new glioma-related circular RNA. Our study aims to explore its functions in glioma tumor progression. Real-time quantitative PCR and western blotting were used to detect RNA and protein abundances. RNase R assay, actinomycin D assay, and subcellular fractionation method were performed to identify the features of circ_0008344. Cell-counting kit-8, 5-ethynyl-2′-deoxyuridine assays, transwell assays, tube formation assay, flow cytometry, and nude mice xenograft tumor model were performed. Target relationship was predicted by bioinformatics algorithms and confirmed by dual-luciferase reporter assay. Abundances of circ_0008344 and SUZ RNA binding domain containing 1 (SZRD1) were highly elevated, while miR-638 was downregulated in glioma tumors and cells. Circ_0008344 was identified as a stable circRNA with a circular structure. Silencing circ_0008344 could restrain glioma proliferation, migration, invasion, and angiogenesis. Circ_0008344 functioned as a sponge for miR-638. The negative regulation of circ_0008344 knockdown on glioma progression and angiogenesis could be reversed by miR-638 inhibitor. SZRD1 was a target of miR-318, and its overexpression overturned the inhibition effect of miR-638 mimic on glioma progression and angiogenesis. Meanwhile, we confirmed that circ_0008344 knockdown inhibited SZRD1 expression, and its effect was reversed by miR-638 inhibitor. Also, circ_00008344 knockdown suppressed glioma tumor growth. Circ_0008344 might contribute to glioma progression through miR-638/SZRD1 axis, which might be a novel pathology and treatment target in glioma.
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References
Cen L, Liu R, Liu W, Li Q, Cui H (2021) Competing endogenous RNA networks in glioma. Front Genet 12(675498). https://doi.org/10.3389/fgene.2021.675498
Chen Z, Duan X (2018) hsa_circ_0000177-miR-638-FZD7-Wnt signaling cascade contributes to the malignant behaviors in glioma. DNA Cell Biol 37(9):791–797. https://doi.org/10.1089/dna.2018.4294
Chiang J, Li X, Liu APY, Qaddoumi I, Acharya S, Ellison DW (2020) Tectal glioma harbors high rates of KRAS G12R and concomitant KRAS and BRAF alterations. Acta Neuropathol 139(3):601–602. https://doi.org/10.1007/s00401-019-02112-x
Chong ZX, Yeap SK, Ho WY (2021) Dysregulation of miR-638 in the progression of cancers. Pathol Res Pract 220(153351). https://doi.org/10.1016/j.prp.2021.153351
Di L, Zhao X, Ding J (2021) Knockdown of circ_0008344 contributes to radiosensitization in glioma via miR-433–3p/RNF2 axis. J Biosci 46(3):1–13
Duffau H, Taillandier L (2015) New concepts in the management of diffuse low-grade glioma: proposal of a multistage and individualized therapeutic approach. Neuro Oncol 17(3):332–342. https://doi.org/10.1093/neuonc/nou153
Geng YB, Pan CC, Xu C, Zuo PC, Wang Y, Li XO, Zhang LW (2020) Long non-coding RNA LINC00346 regulates proliferation and apoptosis by targeting miR-128–3p/SZRD1 axis in glioma. Eur Rev Med Pharmacol Sci 24(18):9581–9590. https://doi.org/10.26355/eurrev_202009_23046
Jiang Y, Zhou J, Zhao J, Zhang H, Li L, Li H, Chen L, Hu J, Zheng W, Jing Z (2020) The U2AF2 /circRNA ARF1/miR-342-3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells. J Exp Clin Cancer Res 39(1):182. https://doi.org/10.1186/s13046-020-01691-y
Latowska J, Grabowska A, Zarebska Z, Kuczynski K, Kuczynska B, Rolle K (2020) Non-coding RNAs in brain tumors, the contribution of lncRNAs, circRNAs, and snoRNAs to cancer development-their diagnostic and therapeutic potential. Int J Mol Sci 21(19). https://doi.org/10.3390/ijms21197001
Li M, Wang J, Liu H (2018) Downregulation of miR-638 promotes progression of breast cancer and is associated with prognosis of breast cancer patients. Onco Targets Ther 11:6871–6877. https://doi.org/10.2147/OTT.S182034
Liu X, Shen S, Zhu L, Su R, Zheng J, Ruan X, Shao L, Wang D, Yang C, Liu Y (2020) SRSF10 inhibits biogenesis of circ-ATXN1 to regulate glioma angiogenesis via miR-526b-3p/MMP2 pathway. J Exp Clin Cancer Res 39(1):121. https://doi.org/10.1186/s13046-020-01625-8
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) Method. Methods 25(4):402–408. https://doi.org/10.1006/meth.2001.1262
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820. https://doi.org/10.1007/s00401-016-1545-1
Mansueto G, Benincasa G, Della Mura N, Nicoletti GF, Napoli C (2020) Epigenetic-sensitive liquid biomarkers and personalised therapy in advanced heart failure: a focus on cell-free DNA and microRNAs. J Clin Pathol 73(9):535–543. https://doi.org/10.1136/jclinpath-2019-206404
Pan X, He T, Peng X, Li H, Zhang F, Lai Y (2020) miR-638 acts as an oncogene and predicts poor prognosis in renal cell carcinoma. Am J Transl Res 12(7):3645–3659
Paulmurugan R, Malhotra M, Massoud TF (2019) The protean world of non-coding RNAs in glioblastoma. J Mol Med (berl) 97(7):909–925. https://doi.org/10.1007/s00109-019-01798-6
Rodriguez-Viciana P, Warne PH, Dhand R, Vanhaesebroeck B, Gout I, Fry MJ, Waterfield MD, Downward J (1994) Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature 370(6490):527–532. https://doi.org/10.1038/370527a0
Saral MA, Tuncer SB, Odemis DA, Erdogan OS, Erciyas SK, Saip P, Ozel S, Yazici H (2021) New biomarkers in peripheral blood of patients with ovarian cancer: high expression levels of miR-16-5p, miR-17-5p, and miR-638. Arch Gynecol Obstet. https://doi.org/10.1007/s00404-021-06138-z
Schittenhelm J, Krischker N, Gepfner-Tuma I, Behling F, Noell S, Eckert F, Biskup S, Tabatabai G (2019) Oncogenic KRAS hotspot mutations are rare in IDH-mutant glioma. Brain Pathol 29(3):321–324. https://doi.org/10.1111/bpa.12709
Sun J, Li B, Shu C, Ma Q, Wang J (2020) Functions and clinical significance of circular RNAs in glioma. Mol Cancer 19(1):34. https://doi.org/10.1186/s12943-019-1121-0
Tang KL, Tang HY, Du Y, Tian T, Xiong SJ (2019) MiR-638 suppresses the progression of oral squamous cell carcinoma through wnt/beta-catenin pathway by targeting phospholipase D1. Artif Cells Nanomed Biotechnol 47(1):3278–3285. https://doi.org/10.1080/21691401.2019.1647222
Wang J, Li T, Wang B (2021) Circ-UBAP2 functions as sponges of miR-1205 and miR-382 to promote glioma progression by modulating STC1 expression. Cancer Med 10(5):1815–1828. https://doi.org/10.1002/cam4.3759
Wang JL, Hu Y, Kong X, Wang ZH, Chen HY, Xu J, Fang JY (2013) Candidate microRNA biomarkers in human gastric cancer: a systematic review and validation study. PLoS ONE 8(9):e73683. https://doi.org/10.1371/journal.pone.0073683
Wang S, Li Q, Wang Y, Li X, Wang R, Kang Y, Xue X, Meng R, Wei Q, Feng X (2018) Upregulation of circ-UBAP2 predicts poor prognosis and promotes triple-negative breast cancer progression through the miR-661/MTA1 pathway. Biochem Biophys Res Commun 505(4):996–1002. https://doi.org/10.1016/j.bbrc.2018.10.026
Wang Y, Gao R, Li J, Tang S, Li S, Tong Q, Mao Y (2020) Circular RNA hsa_circ_0003141 promotes tumorigenesis of hepatocellular carcinoma via a miR-1827/UBAP2 axis. Aging (Albany NY) 12(10):9793–9806. https://doi.org/10.18632/aging.103244
Wu Z, Zheng M, Zhang Y, Xie M, Tian S, Ding T, Li L, Guan Q (2020) Hsa_circ_0043278 functions as competitive endogenous RNA to enhance glioblastoma multiforme progression by sponging miR-638. Aging (Albany NY) 12(21):21114–21128. https://doi.org/10.18632/aging.103603
Xiong X, Rao G, Roy RV, Zhang Y, Means N, Dey A, Tsaliki M, Saha S, Bhattacharyya S, Dhar Dwivedi SK, Rao CV, McCormick DJ, Dhanasekaran D, Ding K, Gillies E, Zhang M, Yang D, Bhattacharya R, Mukherjee P (2020) Ubiquitin-binding associated protein 2 regulates KRAS activation and macropinocytosis in pancreatic cancer. FASEB J 34(9):12024–12039. https://doi.org/10.1096/fj.201902826RR
Xu P, Wang L, Xie X, Hu F, Yang Q, Hu R, Jiang L, Ding F, Mei J, Liu J, Xiao H (2020) Hsa_circ_0001869 promotes NSCLC progression via sponging miR-638 and enhancing FOSL2 expression. Aging (Albany NY) 12(23):23836–23848. https://doi.org/10.18632/aging.104037
Yang C, Zheng J, Xue Y, Yu H, Liu X, Ma J, Liu L, Wang P, Li Z, Cai H, Liu Y (2017) The Effect of MCM3AP-AS1/miR-211/KLF5/AGGF1 axis regulating glioblastoma angiogenesis. Front Mol Neurosci 10:437. https://doi.org/10.3389/fnmol.2017.00437
Yokota Y, Noda T, Okumura Y, Kobayashi S, Iwagami Y, Yamada D, Tomimaru Y, Akita H, Gotoh K, Takeda Y, Tanemura M, Murakami T, Umeshita K, Doki Y, Eguchi H (2021) Serum exosomal miR-638 is a prognostic marker of HCC via downregulation of VE-cadherin and ZO-1 of endothelial cells. Cancer Sci 112(3):1275–1288. https://doi.org/10.1111/cas.14807
Zhang H, Liang H, Wu S, Zhang Y, Yu Z (2021) MicroRNA-638 induces apoptosis and autophagy in human liver cancer cells by targeting enhancer of zeste homolog 2 (EZH2). Environ Toxicol Pharmacol 82:103559. https://doi.org/10.1016/j.etap.2020.103559
Zhao N, Zhang G, He M, Huang H, Cao L, Yin A, Wang P, Wang L (2017) SZRD1 is a novel protein that functions as a potential tumor suppressor in cervical cancer. J Cancer 8(11):2132–2141. https://doi.org/10.7150/jca.18806
Zheng DH, Wang X, Lu LN, Chen DL, Chen JM, Lin FM, Xu XB (2018) MiR-638 serves as a tumor suppressor by targeting HOXA9 in glioma. Eur Rev Med Pharmacol Sci 22(22):7798–7806. https://doi.org/10.26355/eurrev_201811_16404
Zhou J, Wang H, Chu J, Huang Q, Li G, Yan Y, Xu T, Chen J, Wang Y (2018) Circular RNA hsa_circ_0008344 regulates glioblastoma cell proliferation, migration, invasion, and apoptosis. J Clin Lab Anal 32(7):e22454. https://doi.org/10.1002/jcla.22454
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Deng, L., Gong, K. & Wang, G. Hsa_circ_0008344 Promotes Glioma Tumor Progression and Angiogenesis Presumably by Regulating miR-638/SZRD1 Pathway. Neurotox Res 40, 825–836 (2022). https://doi.org/10.1007/s12640-022-00504-8
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DOI: https://doi.org/10.1007/s12640-022-00504-8