Circ-U2AF1 promotes human glioma via derepressing neuro-oncological ventral antigen 2 by sponging hsa-miR-7-5p.

The prognosis for human glioma, a malignant tumor of the central nervous system, is poor due to its rapid growth, genetic heterogeneity, and inadequate understanding of its underlying molecular mechanisms. Circular RNAs composed of exonic sequences, represent an understudied form of noncoding RNAs (ncRNAs) that was discovered more than a decade ago, function as microRNA sponges. We aimed to assess the relationship between circ-U2AF1 (CircRNA ID: hsa_circ_0061868) and hsa-mir-7-5p and examine their effects on proliferation, apoptosis, and the metastatic phenotype of glioma cells regulated by neuro-oncological ventral antigen 2 (NOVA2). We found that the expression levels of circ-U2AF1 and NOVA2 were upregulated, while hsa-miR-7-5p was downregulated in human glioma tissues and glioma cell lines. Our data and bioinformatic analysis indicated the association of these molecules with glioma grade, a positive correlation between circ-U2AF1 and NOVA2 expression levels and a negative correlation of hsa-miR-7-5p with both circ-U2AF1 and NOVA2, respectively. In addition, silencing of circ-U2AF1 expression resulted in increased hsa-miR-7-5p expression and decreased NOVA2 expression both in vitro and in vivo. Luciferase assay confirmed hsa-miR-7-5p as a direct target of circ-U2AF1 and NOVA2 as a direct target of hsa-miR-7-5p. Functionally, silencing of circ-U2AF1 inhibits glioma development by repressing NOVA2 via upregulating hsa-miR-7-5p both in vitro and in vivo. Thus, we assumed that circ-U2AF1 promotes glioma malignancy via derepressing NOVA2 by sponging hsa-miR-7-5p. Taken together, we suggest that circ-U2AF1 can be a prognostic biomarker and the circ-U2AF1/hsa-miR-7-5p/NOVA2 regulatory pathway may be a novel therapeutic target for treating gliomas.

Li G ，Huang M ，Cai Y ，Yang Y ，Sun X ，Ke Y ... -  《-》

Circ_0072088 promotes the development of non-small cell lung cancer via the miR-377-5p/NOVA2 axis.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death globally. This study aimed to disclose the role of circular RNA circ_0072088 in NSCLC and illustrate its potential mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circ_0072088, zinc finger RNA binding protein (ZFR), microRNA-377-5p (miR-377-5p) and NOVA alternative splicing regulator 2 (NOVA2). The viability, colony formation, cell cycle, migration and invasion of NSCLC cells were measured by cell counting kit-8 (CCK8) assay, colony formation assay, flow cytometry, wound healing assay and transwell invasion assay. Western blot assay was employed to examine the protein levels of proliferating cell nuclear antigen (PCNA), Cyclin D1, matrix metallopeptidase 2 (MMP2), MMP9 and NOVA2. The downstream targets of circ_0072088 and miR-377-5p were searched through using circular RNA Interactome and TargetScan databases, and the interaction between miR-377-5p and circ_0072088 or NOVA2 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. in vivo tumor growth assay was used to evaluate the functions of circ_0072088 in the progression of NSCLC in vivo. GSE101586 dataset and the analysis of tissue specimens showed that circ_0072088 was aberrantly upregulated in tumor tissues of lung cancer and NSCLC. Circ_0072088 interference caused marked suppression on the proliferation and motility of NSCLC cells. Circ_0072088 could negatively regulate miR-377-5p through direct combination. Circ_0072088 contributed to the progression of NSCLC through sponging miR-377-5p. MiR-377-5p could directly interact with NOVA2, and the overexpression of NOVA2 overturned miR-377-5p-mediated influence on NSCLC cells. Circ_0072088 facilitated the progression of NSCLC in vivo. Circ_0072088 facilitated the proliferation and metastasis of NSCLC cells through upregulating NOVA2 via functioning as a competitive endogenous RNA (ceRNA) for miR-377-5p.

Tan Z ，Cao F ，Jia B ，Xia L ... -  《-》

Hsa_circ_0076931 suppresses malignant biological properties, down-regulates miR-6760-3p through direct binding, and up-regulates CCBE1 in glioma.

The function of circular RNAs (circRNAs) in gliomas is as yet unknown. The present study explored role of hsa_circ_0076931 in glioma. circRNA expression profiles were identified via RNA-seq followed by qRT-PCR validation in three pairs of glioma and normal brain tissues (NBT). The function of hsa_circ_0076931 was investigated in vitro using cell lines as well as in vivo using a xenograft tumor. Hsa_circ_0076931 was up-regulated by overexpression and an mRNA profile compared with wild-type was identified by RNA-seq. The relationship between miR-6760-3p and hsa_circ_0076931 or CCBE1 was confirmed via luciferase reporter or AGO2-RIP assays. A total of 507 circRNAs were identified in glioma tissues that were differentially expressed compared with that in NBT, and the sequencing data were deposited in BioProject (ID: PRJNA746438). Hsa_circ_0007694 and hsa_circ_0008016 were memorably increased whereas hsa_circ_0076931 and hsa_circ_0076948 decreased in glioma compared with those in NBT. Additionally, hsa_circ_0076931 expression was negatively correlated with histological grade. Overexpression of hsa_circ_0076931 inhibited proliferation, migration, and invasion while promoting apoptosis of glioma cells. A total of 4383 and 537 aberrantly expressed genes were identified between the hsa_circ_0076931-overexpressed and control groups in H4 and U118-MG cells, respectively; the sequencing data were deposited in BioProject (ID: PRJNA746438). These differentially expressed genes were mainly enriched in cancer-related pathways. In addition, elevated hsa_circ_0076931 levels induced the expression of CCBE1 while suppressing miR-6760-3p expression. miR-6760-3p can bind to hsa_circ_0076931. The experimental evidence supports using hsa_circ_0076931 as a marker for glioma and to help prevent malignant progression. The mechanism might be relevant to miR-6760-3p and CCBE1.

Ke Y ，Su S ，Duan C ，Wang Y ，Cao G ，Fang Z ，Tuo Y ，Li W ，Wang Z ，Zhang S ... -  《-》

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 ... -  《-》

Blocking hsa_circ_0006168 suppresses cell proliferation and motility of human glioblastoma cells by regulating hsa_circ_0006168/miR-628-5p/IGF1R ceRNA axis.

Wang T ，Mao P ，Feng Y ，Cui B ，Zhang B ，Chen C ，Xu M ，Gao K ... -  《-》