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

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.

Yin K ，Liu X 《-》

Circular RNA circMMP1 Contributes to the Progression of Glioma Through Regulating TGIF2 Expression by Sponging miR-195-5p.

Glioma is characterized by high morbidity and mortality worldwide. Circular RNA (circRNA) matrix metallopeptidase 1 (circMMP1, hsa_circ_0024108) was reported to be increased in glioma. This study is designed to explore the role and mechanism of circMMP1 in glioma progression. CircMMP1, linear MMP1, microRNA-195-5p (miR-195-5p), and transforming growth factor-beta-induced 2 (TGIF2) level were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein levels of TGIF2, Beclin1, and p62 were examined by Western blot assay. Colony number, migration, invasion, and apoptosis were detected by Colony formation, transwell, and flow cytometry assays, severally. The binding relationship between miR-195-5p and circMMP1 or TGIF2 was predicted by starbase or Targetscan and then verified by a dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. The biological role of circMMP1 on glioma cell growth was examined by the xenograft tumor model in vivo. CircMMP1 and TGIF2 expression were upregulated, and miR-195-5p expression was downregulated in glioma tissues and cells. And the knockdown of circMMP1 could block colony formation, migration, and invasion and expedite apoptosis and autophagy in glioma cells. The mechanical analysis discovered that circMMP1 acted as a sponge of miR-195-5p to regulate TGIF2 expression. CircMMP1 knockdown suppressed cell growth of glioma in vivo. CircMMP1 boosted glioma progression partly by targeting the miR-195-5p/TGIF2 axis, suggesting a promising circRNA-targeted therapy for glioma treatment.

Zhang K ，Wang Q ，Zhao D ，Liu Z ... -  《-》

Circ-0001801 contributes to cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) in glioblastoma by regulating miR-628-5p/HMGB3 axis.

Chen WL ，Jiang L ，Wang JS ，Liao CX ... -  《-》

Circular RNA hsa_circ_0076248 promotes oncogenesis of glioma by sponging miR-181a to modulate SIRT1 expression.

Glioma is one of the most common primary malignancies of the central nervous system, which has aggressive clinical behavior and a poorer prognosis. MicroRNAs (miRs) are a class of small noncoding RNAs that function as mediators of gene expression, which can be sponged by circRNA provided with a closed circular structure. Dysregulations of circular RNAs (circRNAs) and miRs have been implicated in the development and progression of glioma. In the current study, we investigated the role of circular RNA hsa_circ_0076248 in mediating the oncogenesis of glioma by sponging miR-181a to modulate silent information regulator 1 (SIRT1) expression in vitro and in vivo. The quantitative real-time polymerase chain reaction results showed that the expression of miR-181a was significantly decreased in glioma tissues and cell lines compared with normal brain tissues and normal gliocyte, respectively, and the expression of hsa_circ_0076248 and SIRT1 demonstrated the opposite. Bioinformatics analysis identified hsa_circ_0076248 could sponge miR-181a, and miR-181a could target the mRNA of SIRT1. Our results verified that downregulating hsa_circ_0076248 or upregulating miR-181a could depress the proliferation and invasion of glioma in vitro and in vivo. The experiment also showed that downregulating hsa_circ_0076248 or upregulating miR-181a could remarkably promote the temozolomide chemotherapy sensitivity. Furthermore, Western blot analysis testified that downregulating hsa_circ_0076248 or upregulating miR-181a could promote the expression of p53 and SIRT1. In summary, our study sheds light on the regulatory mechanism of hsa_circ_0076248 in glioma growth and invasion via sponging miR-181a, which downregulates the SIRT1 expression and also suggests that hsa_circ_0076248, miR-181a, and SIRT1 may serve as potential therapeutic targets for glioma.

Lei B ，Huang Y ，Zhou Z ，Zhao Y ，Thapa AJ ，Li W ，Cai W ，Deng Y ... -  《-》

The U2AF2 /circRNA ARF1/miR-342-3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells.

Jiang Y ，Zhou J ，Zhao J ，Zhang H ，Li L ，Li H ，Chen L ，Hu J ，Zheng W ，Jing Z ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》