CircRNA circ_POSTN promotes the malignancy of glioma by regulating the miR-433-3p/SPARC axis

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.

Keywords: Glioma; Growth; Metastasis; SPARC; circ_POSTN; miR-433-3p.