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Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas.

ABSTRACT: BACKGROUND:Recent evidences have shown that circular RNAs (circRNAs) are frequently dysregulated and play paramount roles in various cancers. circRNAs are abundant in central nervous system (CNS); however, few studies describe the clinical significance and role of circRNAs in gliomas, which is the most common and aggressive primary malignant tumor in the CNS. METHODS:A bioinformatics analysis was performed to profile and screen the dyregulated circRNAs during early neural development. Quantitative real-time PCR was used to detect the expression of circ-MAPK4 and target miRNAs. Glioma cells were transfected with circ-MAPK4 siRNAs, then cell proliferation, apoptosis, transwell assays, as well as tumorigenesis and TUNEL assays, were performed to examine effect of circ-MAPK4 in vitro and vivo. Biotinylated-circ-MAPK4 probe based pull-down assay was conducted to confirm the relationship between circ-MAPK4 and miR-125-3p. RESULTS:In this study, we identified a circRNA, circ-MAPK4 (has_circ_0047688), which was downregulated during early neural differentiation. In gliomas, circ-MAPK4 acted as an oncogene, was inversely upregulated and linked to clinical pathological stage of gliomas (P?

SUBMITTER: He J

PROVIDER: S-EPMC6986105 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas.

He Jiehua J Huang Zuoyu Z He Mingliang M Liao Jianyou J Zhang Qianqian Q Wang Shengwen S Xie Lin L Ouyang Leping L Koeffler H Phillip HP Yin Dong D Liu Anmin A

Molecular cancer 20200128 1

<h4>Background</h4>Recent evidences have shown that circular RNAs (circRNAs) are frequently dysregulated and play paramount roles in various cancers. circRNAs are abundant in central nervous system (CNS); however, few studies describe the clinical significance and role of circRNAs in gliomas, which is the most common and aggressive primary malignant tumor in the CNS.<h4>Methods</h4>A bioinformatics analysis was performed to profile and screen the dyregulated circRNAs during early neural developm ...[more]

PMID: 31992303

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Project description:ObjectiveCirc-centro-some/spindle pole-associated protein (CSPP1) has been confirmed to be characterized in diverse human malignancies and its ectopic expression may regulate tumor progression and development. However, in hepatocellular carcinoma (HCC), its biological role, clinical significance and molecular mechanism are still unclear.MethodsCirc-CSPP1 expression and its prognostic values in HCC tissues were detected by qRT-PCR or in situ hybridization (ISH), and enriched by using Rnase R. The functional experiments (Circ-CSPP1 was overexpressed or knocked down) were performed in HCC cells. The HCC cell growth was analyzed by CCK-8 assay, transwell, wound healing and colony formation assays. The interation between circ-CSPP1 and miR-577/miR-577 and cyclin E2 (CCNE2) were determined by dual luciferase assay or RNA binding protein immunoprecipitation (RIP) assay. The RNA fluorescence in situ hybridization (FISH) assay was used to detect the subcellular distribution. Finally, an in vivo nude mouse tumor model was constructed.ResultsIn HCC patients and cells, circ-CSPP1 was aberrantly expressed, and its upregulation predicted poor prognosis, and closely correlated with tumor size and TNM stage. Circ-CSPP1 resisted RnaseR digestion, indicating it is a circular RNA structure. Moreover, overexpression of circ-CSPP1 promoted HCC cell viability, colony formation, migration, and invasion in vitro. Knockdown of circ-CSPP1 showed contrary results. Circ-CSPP1 acts as a miR-577 sponge and positively regulated the target of miR-577, CCNE2. Besides, miR-577 inhibitor rescued the suppressive effects of circ-CSPP1 knockdown on HCC cell growth, whereas was completely reversed by silencing of CCNE2. Finally, the in vivo experiments confirmed that circ-CSPP1 knockdown regulated xenograft tumor volume and downregulated CCNE2, p-Rb, E2F1 and c-myc expression.ConclusionThese findings revealed that circ-CSPP1 contributed to HCC progression by positively regulating CCNE2 via miR-577, thus established its potential as new a prognostic and therapeutic marker for HCC patients.

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Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas.

Publications

Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas.

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