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Circular RNA hsa_circ_0005114-miR-142-3p/miR-590-5p-adenomatous polyposis coli protein axis as a potential target for treatment of glioma.

ABSTRACT: Glioma is the most common type of brain tumor and is associated with a high mortality rate. Despite recent advances in treatment options, the overall prognosis in patients with glioma remains poor. Studies have suggested that circular (circ)RNAs serve important roles in the development and progression of glioma and may have potential as therapeutic targets. However, the expression profiles of circRNAs and their functions in glioma have rarely been studied. The present study aimed to screen differentially expressed circRNAs (DECs) between glioma and normal brain tissues using sequencing data collected from the Gene Expression Omnibus database (GSE86202 and GSE92322 datasets) and explain their mechanisms based on the competing endogenous (ce)RNA regulatory hypothesis. In total, 424 commonly downregulated DECs (with the Gene_symbol annotated in the circBase database) in these two datasets were identified. Using the CircInteractome and Starbase databases, 18 micro (mi)RNAs (miRs) were predicted to interact with DECs, while 22 glioma-related genes obtained from the Comparative Toxicogenomics Database were predicted to be regulated by 15 miRNAs via the miRwalk 2.0 database. A ceRNA network was established based on 115 DECs, 15 miRNAs and 22 mRNAs. LinkedOmics online analysis using The Cancer Genome Atlas (TCGA) data showed that hsa-miR-142-3p/hsa-miR-590-5p and their target gene adenomatous polyposis coli protein (APC) were all significantly associated with overall survival rate and their prognosis trend was opposite, revealing that high expression levels of hsa-miR-142-3p/hsa-miR-590-5 were associated with a poor overall survival rate, while high APC expression with a good overall survival rate. UALCAN analysis using TCGA data of glioblastoma multiforme and the GSE25632 and GSE103229 microarray datasets showed that hsa-miR-142-3p/hsa-miR-590-5p was upregulated and APC was downregulated. Thus, hsa-miR-142-3p/hsa-miR-590-5p-APC-related circ/ceRNA axes may be important in glioma, and hsa_circ_0005114 interacted with both of these miRNAs. Functional analysis showed that hsa_circ_0005114 was involved in insulin secretion, while APC was associated with the Wnt signaling pathway. In conclusion, hsa_circ_0005114-miR-142-3p/miR-590-5p-APC ceRNA axes may be potential targets for the treatment of glioma.

SUBMITTER: Wei B

PROVIDER: S-EPMC7709550 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Circular RNA hsa_circ_0005114-miR-142-3p/miR-590-5p-adenomatous polyposis coli protein axis as a potential target for treatment of glioma.

Wei Bo B Wang Le L Zhao Jingwei J

Oncology letters 20201119 1

Glioma is the most common type of brain tumor and is associated with a high mortality rate. Despite recent advances in treatment options, the overall prognosis in patients with glioma remains poor. Studies have suggested that circular (circ)RNAs serve important roles in the development and progression of glioma and may have potential as therapeutic targets. However, the expression profiles of circRNAs and their functions in glioma have rarely been studied. The present study aimed to screen diffe ...[more]

PMID: 33281969

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Project description:BackgroundColorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Exosome shave emerged as crucial regulators of intercellular communication and that abundant Circular RNAs (circRNAs) are enriched within exosomes. CircRNAs are novel members of noncoding RNAs regulating cancer proliferation and progression. However, the function and regulatory mechanism of cancer-derived exosomal circRNAs in CRC remains unclear.MethodsCRC cells-derived exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blot. CCK-8, wound healing and transwell assays, and flow cytometry assays were conducted to assess whether exosomes would affect the proliferation, metastasis, and apoptosis of CRC cells, respectively. Moreover, we performed the RNA sequencing and RT-qPCR to identify circRNAs in exosome-stimulated CRC cells. Fluorescence in situ hybridization (FISH) assay was used to detect the cellular distribution of circPACRGL. Bioinformatic analyses (StarBase 2.0) were used to pool the miRNA targets of circPACRGL. Luciferase assays were performed to verify the direct interaction. Finally, flow cytometry was used to detect the differentiation of N1-N2 neutrophils.ResultsOur study identified a novel CRC-derived exosomal circRNA, circPACRGL. We found circPACRGL was significantly upregulated in CRC cells after tumor-derived exosomes addition. Moreover, circPACRGL serves as a sponge for miR-142-3p/miR-506-3p to facilitate the transforming growth factor-β1 (TGF-β1) expression. As a result, circPACRGL promoted CRC cell proliferation, migration and invasion, as well as differentiation of N1 to N2 neutrophils via miR-142-3p/miR-506-3p-TGF-β1 axis.ConclusionOur study, the first to reveal that cancer-derived exosomal circPACRGL plays an oncogenic role in CRC proliferation and metastasis, providing mechanistic insights into the roles of circRNAs in CRC progression and a valuable marker for CRC treatment.

Dataset Information

Circular RNA hsa_circ_0005114-miR-142-3p/miR-590-5p-adenomatous polyposis coli protein axis as a potential target for treatment of glioma.

Publications

Circular RNA hsa_circ_0005114-miR-142-3p/miR-590-5p-adenomatous polyposis coli protein axis as a potential target for treatment of glioma.

Similar Datasets

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