CircMMP1 promotes the progression of glioma through miR-433/HMGB3 axis in vitro and in vivo

Abstract

Circular RNAs (circRNAs) are non-coding RNAs that have shown to regulate the progression of human diseases, including a variety of cancers. We aimed to investigate the function and the underlying working mechanism of circRNA matrix metallopeptidase 1 (circMMP1; hsa_circ_0024108) in glioma progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of circMMP1, microRNA-433-3p (written as "miR-433") and high mobility group box 3 (HMGB3). Nanoparticle tracking analysis (NTA) was used to analyze the relative concentration and size distribution of serum exosomes. Cell proliferation was analyzed via cell counting kit-8 (CCK8) assay and colony formation assay. Transwell migration and invasion assays were used to examine the metastasis ability of glioma cells. Cell apoptosis was assessed by flow cytometry. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to verify the interactions of circMMP1/miR-433 and miR-433/HMGB3 messenger RNA (mRNA). Xenograft mouse model was built to clarify the role of circMMP1 in vivo. The results showed that high serum exosomal circMMP1 level might predict poor prognosis of glioma patients. CircMMP1 promoted the proliferation and motility and impeded the apoptosis of glioma cells. MiR-433 was a direct target of circMMP1, and circMMP1 silencing-mediated influences in glioma cells were partly alleviated by the knockdown of miR-433. MiR-433 directly interacted with HMGB3 mRNA, and HMGB3 overexpression partly counteracted the effects of miR-433 up-regulation in glioma cells. CircMMP1 enhanced HMGB3 level through sponging miR-433 in glioma cells. CircMMP1 silencing suppressed the progression of glioma in vivo. CircMMP1 promoted the progression of glioma through acting as a competitive endogenous RNA (ceRNA) of miR-433 to up-regulate HMGB3. CircMMP1 level in serum exosomes might be a potential marker for the diagnosis of glioma patients. Targeting circMMP1/miR-433/HMGB3 signaling might be a novel insight for glioma treatment.

Keywords: HMGB3; circMMP1; exosome; glioma; miR-433.