MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change
Tóm tắt
RNA binding proteins (RBPs) have been reported to interact with RNAs to regulate gene expression. Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs, which involved in the angiogenesis of tumor. The purpose of this study is to elucidate the potential roles and molecular mechanisms of MOV10 and circ-DICER1 in regulating the angiogenesis of glioma-exposed endothelial cells (GECs). The expressions of circ-DICER1, miR-103a-3p and miR-382-5p were detected by real-time PCR. The expressions of MOV10, ZIC4, Hsp90 and PI3K/Akt were detected by real-time PCR or western blot. The binding ability of circ-SHKBP1 and miR-544a / miR-379, ZIC4 and miR-544a / miR-379 were analyzed with Dual-Luciferase Reporter System or RIP experiment. The direct effects of ZIC4 on the Hsp90β promoter were analyzed by the ChIP experiment. The cell viability, migration and tube formation in vitro were detected by CCK-8, Transwell assay and Matrigel tube formation assay. The angiogenesis in vivo was evaluated by Matrigel plug assay. Student’s t-test (two tailed) was used for comparisons between two groups. One-way analysis of variance (ANOVA) was used for multi-group comparisons followed by Bonferroni post-hoc analysis. The expressions of RNA binding proteins MOV10, circ-DICER1, ZIC4, and Hsp90β were up-regulated in GECs, while miR103a-3p/miR-382-5p were down-regulated. MOV10 binding circ-DICER1 regulated the cell viability, migration, and tube formation of GECs. And the effects of both MOV10 and circ-DICER1 silencing were better than the effects of MOV10 or circ-DICER1 alone silencing. In addition, circ-DICER1 acts as a molecular sponge to adsorb miR-103a-3p / miR-382-5p and impair the negative regulation of miR-103a-3p / miR-382-5p on ZIC4 in GECs. Furthermore, ZIC4 up-regulates the expression of its downstream target Hsp90β, and Hsp90 promotes the cell viability, migration, and tube formation of GECs by activating PI3K/Akt signaling pathway. MOV10 / circ-DICER1 / miR-103a-3p (miR-382-5p) / ZIC4 pathway plays a vital role in regulating the angiogenesis of glioma. Our findings not only provides novel mechanisms for the angiogenesis of glioma, but also provide potential targets for anti-angiogenesis therapies of glioma.
Tài liệu tham khảo
Omuro A, Deangelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA. 2013;310(17):1842–50.
Stupp R, Hegi Me, Mason Wp, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459–66.
Bello L, Giussani C, Carrabba G, et al. Angiogenesis and invasion in gliomas. Cancer Treat Res. 2004;117:263–84.
Rk Jain, Ed Tomaso, Dg Duda, et al. Angiogenesis in brain tumours. Nat Rev Neurosci. 2007;8(8):610–22.
Castello A, Fischer B, Eichelbaum K, et al. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell. 2012;149(6):1393–406.
Darnell Rb. RNA regulation in neurologic disease and cancer. Cancer Res Treat 2010;42(3):125–129.
Granneman S, Petfalski E, Swiatkowska A, et al. Cracking pre-40S ribosomal subunit structure by systematic analyses of RNA-protein cross-linking. EMBO J. 2010;29(12):2026–36.
Tp Chendrimada, Kj Finn, K Ji, et al. MicroRNA silencing through RISC recruitment of eIF6. Nature. 2007;447(7146):823–8.
Nakano M, Kakiuchi Y, Shimada Y, et al. MOV10 as a novel telomerase-associated protein. Biochem Biophys Res Commun. 2009;388(2):328–32.
Kumar L Shamsuzzama, Haque R, et al. Circular RNAs: the emerging class of non-coding RNAs and their potential role in human neurodegenerative diseases. Mol Neurobiol. 2017;54(9):7224–34.
Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495(7441):333–8.
Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 2015;22(3):256–64.
Martello G, Rosato A, Ferrari F, et al. A MicroRNA targeting dicer for metastasis control. Cell. 2010;141(7):1195–207.
Ma Z, Swede H, Cassarino D, et al. Up-regulated dicer expression in patients with cutaneous melanoma. PLoS One. 2011;6(6):e20494.
Wm Merritt, Yg Lin, Ly Han, et al. Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med. 2008;359(25):2641–50.
Dp Bartel. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.
Wang X, Lin Y, Peng L, et al. MicroRNA-103 promotes proliferation and inhibits apoptosis in spinal osteosarcoma cells by targeting p57. Oncol Res. 2018. https://doi.org/10.3727/096504017X15144741233346.
Yu M, Xue Y, Zheng J, et al. Linc00152 promotes malignant progression of glioma stem cells by regulating miR-103a-3p/FEZF1/CDC25A pathway. Mol Cancer. 2017;16(1):110.
Vastrad B, Vastrad C, Godavarthi A, et al. Molecular mechanisms underlying gliomas and glioblastoma pathogenesis revealed by bioinformatics analysis of microarray data. Med Oncol. 2017;34(11):182.
Wilson R, Espinos-Diez C, Kanner N, et al. MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment. Nat Commun. 2016;7:13597.
Chen T, Ren H, Thakur A, et al. miR-382 inhibits tumor progression by targeting SETD8 in non-small cell lung cancer. Biomed Pharmacother. 2017;86:248–53.
Zhou B, Song J, Han T, et al. MiR-382 inhibits cell growth and invasion by targeting NR2F2 in colorectal cancer. Mol Carcinog. 2016;55(12):2260–7.
Seok Jk, Lee Sh, Kim Mj, et al. MicroRNA-382 induced by HIF-1alpha is an angiogenic miR targeting the tumor suppressor phosphatase and tensin homolog. Nucleic Acids Res. 2014,42(12):8062-72.
Aruga J. The role of Zic genes in neural development. Mol Cell Neurosci. 2004;26(2):205–21.
Aruga J, Nozaki Y, Hatayama M, et al. Expression of ZIC family genes in meningiomas and other brain tumors. BMC Cancer. 2010;10:79.
Neckers L. Heat shock protein 90: the cancer chaperone. J Biosci. 2007;32(3):517–30.
Meng J, Liu Y, Han J, et al. Hsp90beta promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma. Mol Cancer. 2017;16(1):72.
Di K, Keir ST, Alexandru-Abrams D, et al. Profiling Hsp90 differential expression and the molecular effects of the Hsp90 inhibitor IPI-504 in high-grade glioma models. J Neuro-Oncol. 2014;120(3):473–81.
Malinda Km. In vivo matrigel migration and angiogenesis assay. Methods Mol Biol. 2009;467:287–94.
Conn Sj, Pillman Ka Toubia J, et al. The RNA binding protein quaking regulates formation of circRNAs. Cell. 2015;160(6):1125–34.
Du Ww, Yang W, Liu E, et al. Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res. 2016;44(6):2846–58.
Cuevas Ra, Ghosh A, Wallerath C, et al. MOV10 provides antiviral activity against RNA viruses by enhancing RIG-I-MAVS-independent IFN induction. J Immunol. 2016;196(9):3877–86.
El Ms, Nicholls J, Maertens GN, et al. Role for the MOV10 RNA helicase in polycomb-mediated repression of the INK4a tumor suppressor. Nat Struct Mol Biol. 2010;17(7):862–8.
Wang W, Snyder N, Worth AJ, et al. Regulation of lipid synthesis by the RNA helicase Mov10 controls Wnt5a production. Oncogene. 2015;4:e154.
Xia W, Qiu M, Chen R, et al. Circular RNA has_circ_0067934 is upregulated in esophageal squamous cell carcinoma and promoted proliferation. Sci Rep. 2016;6:35576.
Li P, Chen S, Chen H, et al. Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chim Acta. 2015;444:132–6.
He Q, Zhao L, Liu Y, et al. Circ-SHKBP1 Regulates the Angiogenesis of U87 Glioma-Exposed Endothelial Cells through miR-544a/FOXP1 and miR-379/FOXP2 Pathways. Mol Ther Nucleic Acids. 2018;10:331–48.
Yang P, Qiu Z, Jiang Y, et al. Silencing of cZNF292 circular RNA suppresses human glioma tube formation via the Wnt/beta-catenin signaling pathway. Oncotarget. 2016;7(39):63449–55.
Zheng Q, Bao C, Guo W, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016;7:11215.
Zheng J, Liu X, Xue Y, et al. TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1beta/Derlin-1 pathway. J Hematol Oncol. 2017;10(1):52.
Zhong Z, Lv M, Chen J. Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma. Sci Rep. 2016;6:30919.
Ma Z. Downregulation of SETD8 by miR-382 is involved in glioma progression. Pathol Res Pract. 2018;214(3):356–60.
Chen Z, Lai Tc, Jan Yh, et al. Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis. J Clin Invest. 2013;123(3):1057–67.
Zhang S, Ge W, Zou G, et al. MiR-382 targets GOLM1 to inhibit metastasis of hepatocellular carcinoma and its down-regulation predicts a poor survival. Am J Cancer Res. 2018;8(1):120–31.
Zhao L, Sun H, Kong H, et al. The Lncrna-TUG1/EZH2 Axis promotes pancreatic Cancer cell proliferation, migration and EMT phenotype formation through sponging Mir-382. Cell Physiol Biochem. 2017;42(6):2145–58.
Fang Y, Xie T, Xue N, et al. miR-382 Contributes to Renal Tubulointerstitial Fibrosis by Downregulating HSPD1. Oxid Med Cell Longev. 2017;2017:4708516.
Bataller L, Wade Df, Fuller Gn, et al. Cerebellar degeneration and autoimmunity to zinc-finger proteins of the cerebellum. Neurology. 2002;59(12):1985–7.
Df Nathan, Mh Vos, S Lindquist. In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone. Proc Natl Acad Sci U S A. 1997;94(24):12949–56.
Maloney A, Workman P. HSP90 as a new therapeutic target for cancer therapy: the story unfolds. Expert Opin Biol Ther. 2002;2(1):3–24.
Sanderson S, Valenti M, Gowan S, et al. Benzoquinone ansamycin heat shock protein 90 inhibitors modulate multiple functions required for tumor angiogenesis. Mol Cancer Ther. 2006;5(3):522–32.
Zhang S, Sun Y, Yuan Z, et al. Heat shock protein 90beta inhibits apoptosis of intestinal epithelial cells induced by hypoxia through stabilizing phosphorylated Akt. BMB Rep. 2013;46(1):47–52.