Abstract
Glioma is a common tumor in the brain. CircRNA hsa_circ_0030018, also termed as hsa_circPOSTN_001 (circ_POSTN), is reported to exert a promoting influence on the development of glioma. Our study intends to deeply explore its regulation mechanism of circ_POSTN. Expression of circ_POSTN, microRNA-433-3p (miR-433-3p) and Secreted protein acidic and rich in cysteine (SPARC) was detected by qRT-PCR or western blot assay. The function of circ_POSTN was analyzed by loss-of-function experiments. The targeting relationship between miR-433-3p and circ_POSTN or SPARC was predicted by bioinformatics analysis and validated by dual-luciferase reporter assay. Xenograft modeling was employed to validate the function of circ_POSTN in glioma in vivo. circ_POSTN and SPARC were upregulated while miR-433-3p was downregulated in glioma tissues and cells. Both circ_POSTN and SPARC knockdown inhibited clonogenicity, migration, and promoted apoptosis of glioma cells. Circ_POSTN sponged miR-433-3p to regulate SPARC expression. Gain of SPARC largely attenuated circ_POSTN knockdown or miR-433-3p overexpression-mediated effects on glioma cell clonogenicity, migration, and apoptosis. Furthermore, silencing of circ_POSTN decreased xenograft tumor growth in vivo. Inhibition of circ_POSTN repressed glioma development, at least in part, via regulating the miR-433-3p/SPARC axis, providing evidence for circ_POSTN as a potential therapeutic target for glioma.
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Xiangting Hua conceived and designed the study, and drafted the first draft of the manuscript. All experiments were completed by all authors. Chaoyong Zhang, Yongfeng Ba, Shiwei Zhao, Kui Fan, Bin Wang analyzed and collated the results. All authors reviewed and critiqued the manuscript, and agreed to the final submission of the manuscript. All authors read and approved the final manuscript.
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Supplementary Information
Supplementary Fig. 1
RIP assay was executed for analysis of the interaction between circ_POSTN or SPARC and miR-433-3p. (A and B) QRT-PCR detection of the abundance of circ_POSTN and miR-433-3p in Ago2 and IgG immunoprecipitates. (C and D) QRT-PCR evaluation of the abundance of miR-433-3p and SPARC mRNA in Ago2 and IgG immunoprecipitates. ***P < 0.001 (PNG 146 kb)
Supplementary Fig. 2
(A) Transfection efficiency of three siRNAs (si-circ_POSTN#1, si-circ_POSTN#2, and si-circ_POSTN#3). (B-D) Pearson correlation analysis was used to assess the correlation among circ_POSTN, miR-433-3p and SPARC in xenograft tumors. ***P < 0.001 (PNG 79 kb)
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Hua, X., Zhang, C., Ba, Y. et al. CircRNA circ_POSTN promotes the malignancy of glioma by regulating the miR-433-3p/SPARC axis. Metab Brain Dis 38, 543–555 (2023). https://doi.org/10.1007/s11011-022-01126-x
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DOI: https://doi.org/10.1007/s11011-022-01126-x