MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change

Abstract

BackgroundRNA 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).MethodsThe 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.ResultsThe 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.ConclusionsMOV10 / 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.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0990-1) contains supplementary material, which is available to authorized users.

Circular RNA USP1 regulates the permeability of blood‐tumour barrier via miR‐194‐5p/FLI1 axis

“…Recently, abnormal circRNA expressions have been demonstrated in various cardiovascular diseases and cancers, which are related to vascular dysfunction. [6][7][8] Knockdown of cZNF609, which is highly enriched in endothelial cells, diminished retinal vessel loss and inhibited pathological angiogenesis in vivo. 9 CircRNA USP1 (circ-USP1, also known as hsa_circ_0000080 according to circBase), which is located at chr1p31, is derived from the back-splicing of exon 6-8 of ubiquitin-specific peptidase 1 (USP1) gene.…”

TRA2A-induced upregulation of LINC00662 regulates blood-brain barrier permeability by affecting ELK4 mRNA stability in Alzheimer’s microenvironment

“…RBP QKI is highly expressed in ECs and promotes the mRNA of β-catenin and VE-cadherin translation by binding with them, which contributes to maintenance of endothelial barrier function [39] . RBPs MOV10 and FUS regulate vascular endothelial function by binding to Circular RNAs (circRNAs) [40,41] .…”

Circular RNAs in the tumour microenvironment

“…In addItion to VEGF, other angiogenic factors may also affect CAEs directly or indirectly [76][77][78][79][80][81]. Recent studies reveal that glioma-exposed endothelial cells (GECs) exhibit high expression of circRNA DICER1 (circ-DICER1) and its RBP MOV10 [82]. Of note, circ-DICER1 could sponge miR-103a-3p/miR-382-5p and attenuated the negative regulation of Zic family member 4 (ZIC4), thus mediating cell proliferation, migration and angiogenesis of GECs [82].…”

“…Recent studies reveal that glioma-exposed endothelial cells (GECs) exhibit high expression of circRNA DICER1 (circ-DICER1) and its RBP MOV10 [82]. Of note, circ-DICER1 could sponge miR-103a-3p/miR-382-5p and attenuated the negative regulation of Zic family member 4 (ZIC4), thus mediating cell proliferation, migration and angiogenesis of GECs [82]. This molecular axis of MOV10/circ-DICER1/miR-103a-3p/miR-382-5p/ZIC4 gives novel insights into glioma angiogenesis, providing prospective targets for anti-angiogenesis strategy [82].…”

“…Of note, circ-DICER1 could sponge miR-103a-3p/miR-382-5p and attenuated the negative regulation of Zic family member 4 (ZIC4), thus mediating cell proliferation, migration and angiogenesis of GECs [82]. This molecular axis of MOV10/circ-DICER1/miR-103a-3p/miR-382-5p/ZIC4 gives novel insights into glioma angiogenesis, providing prospective targets for anti-angiogenesis strategy [82]. Another circRNA axises linked to glioma tumourigenesis and angiogenesis are the circ-SHKBP1/miR-544a/FOXP1 and circ-SHKBP1/miR-379/FOXP2 pathway [83].…”