SRSF10 inhibits biogenesis of circ-ATXN1 to regulate glioma angiogenesis via miR-526b-3p/MMP2 pathway

Abstract

Background: Angiogenesis plays an important role in the progress of glioma. RNA-binding proteins (RBPs) and circular RNAs (circRNAs), dysregulated in various tumors, have been verified to mediate diverse biological behaviors including angiogenesis. Methods: Quantitative real-time PCR (qRT-PCR) and western blot were performed to detect the expression of SRSF10, circ-ATXN1, miR-526b-3p, and MMP2/VEGFA. The potential function of SRSF10/circ-ATXN1/miR-526b-3p axis in glioma-associated endothelial cells (GECs) angiogenesis was further studied. Results: SRSF10 and circ-ATXN1 were significantly upregulated in GECs compared with astrocyte-associated endothelial cells (AECs). Knockdown of SRSF10 or circ-ATXN1 significantly inhibited cell viability, migration and tube formation of GECs where knockdown of SRSF10 exerted its function by inhibiting the formation of circ-ATXN1. Moreover, the combined knockdown of SRSF10 and circ-ATXN1 significantly enhanced the inhibitory effects on cell viability, migration and tube formation of GECs, compared with knockdown of SRSF10 and circ-ATXN1, respectively. MiR-526b-3p was downregulated in GECs. Circ-ATXN1 functionally targeted miR-526b-3p in an RNA-induced silencing complex. Up-regulation of miR-526b-3p inhibited cell viability, migration and tube formation of GECs. Furthermore, miR-526b-3p affected the angiogenesis of GECs via negatively regulating the expression of MMP2/ VEGFA. Conclusion: SRSF10/circ-ATXN1/miR-526b-3p axis played a crucial role in regulating the angiogenesis of GECs. The above findings provided new targets for anti-angiogenic therapy in glioma.

CircASH2L Promotes Ovarian Cancer Tumorigenesis, Angiogenesis, and Lymphangiogenesis by Regulating the miR-665/VEGFA Axis as a Competing Endogenous RNA

“…Increasing evidence has shown that circRNAs, such as circASH2L (Chen et al, 2019), circHIPK3 (Wang et al, 2019b), circMET (Pei et al, 2020), circATXN1 (Liu X. et al, 2020), circZNF566 , circFMN2 (Shan et al, 2020), circCYFIP2 (Lin et al, 2020), and circWHSC1 (Zong et al, 2019), have essential functions in cancer biology and are potential biomarkers and treatment targets. We determined the expression of the eight star circRNAs in ovarian cancer and found that circASH2L was the only one expressed differently in our samples ( Figure 1A).…”

Circular RNA CircNOLC1, Upregulated by NF-KappaB, Promotes the Progression of Prostate Cancer via miR-647/PAQR4 Axis

“…Recent reports revealed that circRNAs exert their biological functions mainly relying on the miRNA sponging ( Hansen et al, 2011 , 2013 ). Besides, circRNAs could also play a role in interacting with RNA binding proteins (RBPs) ( Liu et al, 2020 ). In PCa, circRNAs, such as, circ_0007494 and circFMN2, have been recognized to function as competing endogenous RNAs (ceRNAs) to relieve the inhibition of miRNA targets ( Shan et al, 2020 ; Zhang et al, 2020 ).…”

AGAP2-AS1 May Promote the Occurrence and Development of Glioblastoma by Sponging miR-9-5p: Evidence From a ceRNA Network

“…As reported in the literature, MMP2 and MMP9 are closely related to vasculogenic mimicry formation in gliomas (42). Thus, by regulating the MMP2-related pathway, glioma angiogenesis could be inhibited (43). Meanwhile, the regulation of MMP9 activity was shown to be correlated with tumor cell invasion (44).…”