Circular RNA circitga7 accelerates glioma progression via miR-34a-5p/VEGFA axis.
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ABSTRACT:
SUBMITTER: Qi L
PROVIDER: S-EPMC8148479 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Circular RNAs (circRNAs) are a novel category of non-coding RNAs, and they have been identified to participate in glioma tumorigenesis. Here we investigated the functions of circRNA circSCAF11 in glioma genesis, and we unveiled its molecular mechanism in the pathophysiological process. Expression levels of circSCAF11, miR-421, and SP1 mRNA were measured using RT-PCR. Proteins were measured using western blotting. The tumor phenotypes of glioma cells were detected using flow cytometry and Cell Counting Kit-8 (CCK-8), transwell, and xenograft mouse assays. The combination within circSCAF11, miR-421, and SP1 was validated using luciferase reporter assay or RNA pull-down assay. The binding of transcription factor SP1 with vascular endothelial cell growth factor A (VEGFA) promoter was inspected using chromatin immunoprecipitation (ChIP). circSCAF11 expression was found to be significantly upregulated in the glioma tissue specimens and cell lines. The ectopic overexpression of circSCAF11 was closely correlated with the poor clinical outcome of glioma patients. Functionally, knockdown of circSCAF11 inhibited the proliferation, invasion, and tumor growth and induced the G0/G1 phase arrest. Mechanically, circSCAF11 positively regulated the SP1 expression through sponging miR-421. Moreover, transcription factor SP1 activated the transcription of VEGFA, constructing the circSCAF11/miR-421/SP1/VEGFA axis in the glioma genesis. The findings in this research illustrate that circSCAF11 accelerates glioma tumorigenesis through the miR-421/SP1/VEGFA axis, providing a potential target for circRNA and glioma treatment.
| S-EPMC6700438 | biostudies-literature
Project description:Circular RNAs (circRNAs) are group of noncoding RNAs derived from back-splicing events. Accumulating evidence certifies the critical roles of circRNAs in human tumorigenesis. However, the role and biogenesis of circRNAs in cervical cancer are still unclear. Here, a novel identified circRNA, circSLC26A4, was found to be upregulated in cervical cancer tissue and cells. Clinically, the high expression of circSLC26A4 was related to the poor survival of cervical cancer patients. Functionally, cellular experiments indicated that circSLC26A4 knockdown repressed the proliferation, invasion, and tumor growth in vitro and in vivo. Furthermore, circSLC26A4 acted as the sponge of miR-1287-5p; moreover, miR-1287-5p targeted the 3' UTR of HOXA7 mRNA. Mechanistically, RNA binding protein (RBP) quaking (QKI) was identified to interact with the QKI response elements (QREs) in SLC26A4 gene introns, thereby promoting circSLC26A4 biogenesis. In conclusion, these findings demonstrate that circSLC26A4 facilitates cervical cancer progression through the QKI/circSLC26A4/miR-1287-5p/HOXA7 axis, which might bring novel therapeutic strategies for cervical cancer.
| S-EPMC6940609 | biostudies-literature
Project description:Objective: The present study aimed to explore the association between NFIX circular RNA (circNFIX) and miR-34a-5p in glioma. Furthermore, this study investigated the influence that circNFIX has on glioma progression through the upregulation of NOTCH1 via the Notch signaling pathway by sponging miR-34a-5p. Methods: We applied five methods, CIRCexplorer2, circRNA-finder, CIRI, find-circ and MapSplice2, to screen for circRNAs with differential expression between three glioma tissue samples and three paired normal tissue samples. The GSEA software was used to confirm whether significantly different pathways were activated or inactivated in glioma tissues. The binding sites between circNFIX and miR-34a-5p were confirmed by TargetScan. QRT-PCR and western blot were used to measure the relative expression levels of circNFIX, miR-34a-5p and NOTCH and identify their correlation in glioma. RNA immunoprecipitation (RIP) validated the binding relationship between circNFIX and miR-34a-5p, while the targeted relationship between NOTCH1 and miR-34a-5p was verified by a dual luciferase reporter assay. Cell viability and mobility were examined by a CCK-8 assay and wound healing assay, and a flow cytometry assay was employed to analyze cell apoptosis. The nude mouse transplantation tumor experiment verified that si-circNFIX exerted a suppressive effect on glioma progression in vivo. Results: Twelve circRNAs were differentially expressed between the tissue types. Of those, circNFIX was the sole circRNA to be overexpressed in glioma among the five methods of finding circRNAs. In addition, the Notch signaling pathway was considerably upregulated in tumor tissues compared with the paired normal brain tissues. It was determined that circNFIX acted as a sponge of miR-34a-5p, a miRNA that targeted NOTCH1. Downregulation of circNFIX and upregulation of miR-34a-5p both inhibited cell propagation and migration. Furthermore, a miR-34a-5p inhibitor neutralized the suppressive effect of si-circNFIX on glioma cells. Si-circNFIX and miR-34a-5p mimics promoted cell apoptosis. Moreover, it was demonstrated in vivo that si-circNFIX could suppress glioma growth by regulating miR-34a-5p and NOTCH1. Conclusion: CircNFIX was markedly upregulated in glioma cells. CircNFIX could regulate NOTCH1 and the Notch signaling pathway to promote glioma progression by sponging miR-34a-5p via the Notch signaling pathway. This finding provided a deeper insight into the function of circNFIX in human glioma cancer progression.
| S-EPMC6058096 | biostudies-literature
Project description:BackgroundCircular RNA hsa_circ_0061395 (circ_0061395) has been reported to accelerate the advancement of hepatocellular carcinoma (HCC). However, the regulatory mechanism by which circ_0061395 modulates the progression of HCC is unclear.MethodsThe morphology and size of exosomes were analyzed by transmission electron microscope (TEM) and nanoparticle-tracking analysis (NTA). Protein levels were detected by western blotting. Expression levels of circ_0061395, microRNA (miR)-877-5p, and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) mRNA were assessed by quantitative real time polymerase chain reaction (qRT-PCR). The proliferation, invasion, migration, cell cycle progression, and apoptosis were analyzed by cell counting kit-8 (CCK-8), plate clone, transwell, or flow cytometry assays. The targeting relationship between circ_0061395 or PIK3R3 and miR-877-5p was verified using the dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. Xenograft assay was performed to confirm the biological function of circ_0061395 in HCC.ResultsCirc_0061395 was upregulated in HCC tissues, serum, cells, and serum-derived exosomes. Circ_0061395 silencing decreased tumor growth in vivo, and induced cell cycle arrest, apoptosis, repressed proliferation, invasion, and migration of HCC cells in vitro. MiR-877-5p was downregulated while PIK3R3 was upregulated in HCC. Circ_0061395 regulated PIK3R3 expression via competitively binding to miR-877-5p. MiR-877-5p inhibitor overturned circ_0061395 knockdown-mediated influence on malignant behaviors of HCC cells. PIK3R3 overexpression reversed the suppressive influence of miR-877-5p mimic on malignant behaviors of HCC cells.ConclusionCirc_0061395 facilitated HCC progression via regulating the miR-877-5p/PIK3R3 axis, providing a new perspective on the advancement of HCC.
| S-EPMC7788978 | biostudies-literature
Project description:Background:Numerous researches have suggested that circular RNAs (circRNAs) play critical functions in bladder cancer (BC) progression. This study aims to investigate the potential roles of circRNA_103809 in regulating BC development. Methods:qRT-PCR was used to analyze gene expression. CCK8 and colony formation were used to analyze cell proliferation. Transwell was utilized to examine cell migration and invasion. Gemcitabine was used to analyze the effect of circRNA_103809 on the chemo-resistance of BC cells. Luciferase reporter assay was performed to detect the RNA interactions. Results:circRNA_103809 was highly expressed in BC tissues and cell lines. CircRNA_103809 high expression was associated with a poor progression in BC patients. CircRNA_103809 knockdown impaired the growth and metastasis of BC cells. Furthermore, circRNA_103809 silencing increased the sensitivity of BC cells to Gemcitabine treatment. CircRNA_103809 was the sponge for miR-516a-5p and promoted FBXL18 expression via restraining miR-516a-5p activity. Conclusion:circRNA_103809 promotes proliferation, migration, invasion and chemo-resistance of BC cells through regulating miR-516a-5p/FBXL18 axis.
| S-EPMC7457878 | biostudies-literature
Project description:An increasing amount of evidence shows that circular RNAs (circRNAs) have critical effects on cancer progression and development; however, the biological function and potential molecular mechanism of circRNAs in hepatocellular carcinoma (HCC) are still unclear. CircRNA sequencing was used to identify differentially expressed circRNAs between HCC tissue and adjacent normal tissue. We found that circ_0001459 expression was significantly elevated in HCC tissue and cell lines. Furthermore, in vitro and in vivo functional experiments were carried out to detect the effects of circ_0001459 on HCC growth and metastasis. Knockdown of circ_0001459 significantly inhibited the proliferation, migration, and invasion of HCC cells, whereas upregulation of circ_0001459 had the opposite effect. Moreover, bioinformatics analysis, dual-luciferase reporter assay, RNA immunoprecipitation, and fluorescence in situ hybridization assays were used to predict and verify the interaction between circ_0001459, miR-6165, and the target gene IGF1R. Downregulation of circ_0001459 decreased IGF1R expression and inhibited epithelial-to-mesenchymal transition, which could be rescued by treatment with a miR-6165 inhibitor. Mechanistically, we revealed that circ_0001459 could sponge miR-6165 and induce the upregulation of its downstream target IGF1R, thus significantly promoting the progression of HCC. Therefore, circ_0001459 could be a new potential therapeutic target for HCC patients.
| S-EPMC9306989 | biostudies-literature
Project description:BackgroundAccumulating evidences have shown that circular RNAs (circRNAs) play important roles in regulating the pathogenesis of cancer. However, the role of circRNAs in gastric cancer (GC) remains largely unclear.MethodsIn this study, we identified a novel upregulated circRNA, hsa_circ_0001829, in chemically induced malignant transformed human gastric epithelial cells using RNA-seq. Subsequent qRT-PCR and ISH assays were performed to detect the expression level of hsa_circ_0001829 in GC cell lines and tissues. Functional roles of hsa_circ_0001829 in GC were then explored by loss- and gain-of- function assays. Bioinformatic prediction and luciferase assay were used to investigate potential mechanisms of hsa_circ_0001829. Finally, the mice xenograft and metastasis models were constructed to assess the function of hsa_circ_0001829 in vivo.ResultsWe found that hsa_circ_0001829 was significantly upregulated in GC tissues and cell lines. Loss- and gain-of- function assays showed that hsa_circ_0001829 promotes GC cells proliferation, migration and invasion, and the affected cell cycle progression and apoptosis rates may account for the effect of hsa_circ_0001829 on GC proliferation. In addition, bioinformatic prediction and luciferase assay showed that hsa_circ_0001829 acts as a molecular sponge for miR-155-5p and that SMAD2 was a target gene of miR-155-5p; moreover, hsa_circ_0001829 sponges miR-155-5p to regulate SMAD2 expression and hsa_circ_0001829 promotes GC progression through the miR-155-5p-SMAD2 pathway. Finally, suppression of hsa_circ_0001829 expression inhibited tumor growth and aggressiveness in vivo.ConclusionTaken together, our findings firstly demonstrated a novel oncogenic role of hsa_circ_0001829 in GC progression through miR-155-5p-SMAD2 axis, and our study may offer novel biomarkers and therapeutic targets for GC.
| S-EPMC7731483 | biostudies-literature
Project description:More and more findings illustrate the critical roles of circular RNA (circRNA) in diabetes mellitus (DM) and its complications. A major pathological characteristic for DM is the apoptosis of endothelial cells (ECs) induced by high glucose (HG), however, the function of circRNA in the ECs' phenotypes is still elusive. Here, this study identified an up-regulated circRNA (circVEGFC) in the HG-induced human umbilical vein endothelial cells (HUVECs). Functionally, knockdown of circVEGFC alleviated the apoptosis and recovered the proliferation in HUVECs induced by HG administration. Mechanistically, circVEGFC functioned as the sponge of miR-338-3p, and miR-338-3p was found to target the 3'-Untranslated Regions (3'-UTR) of hypoxia inducible factor 1 alpha (HIF-1?). HIF-1?, a critical transcription factor in DM, could activate the transcription of vascular endothelial growth factor A (VEGFA) and promote its protein product. In conclusion, these findings reveal the promotion of circVEGFC/miR-338-3p/HIF-1?/VEGFA axis in the HG-induced ECs' apoptosis, providing a potential treatment strategy for ECs' damage in DM.
| S-EPMC7425483 | biostudies-literature
Project description:Patients with advanced prostate cancer (PCa) have poor prognosis. Circular RNAs (circRNAs) regulate biological processes in a variety of cancers, but the precise roles of circRNAs in PCa are poorly understood. Herein, we identified a novel circRNA, termed circMBOAT2 (has_circ_0007334), which was significantly overexpressed in PCa tissues and cell lines. Overexpression of circMBOAT2 was associated with high Gleason score, advanced pathological T stage, and poor prognosis. Overexpression of circMBOAT2 promoted proliferation, migration, and invasion of PCa cells in vitro, and enhanced tumorigenesis and metastasis in vivo. Mechanistically, circMBOAT2 overexpression upregulated the expression of mTOR by acting as a decoy for miR-1271-5p, resulting in the activation of the PI3K/Akt pathway, ultimately promoting the progression of PCa. Importantly, application of an inhibitor of mTOR significantly antagonized circMBOAT2-mediated PCa tumorigenesis in vivo. circMBOAT2 promotes proliferation and metastasis of PCa through miR-1271-5p/mTOR axis-mediated activation of the PI3K/Akt pathway. In summary, our findings uncover a molecular mechanism in the progression of PCa and indicate that circMBOAT2 may be a useful prognostic biomarker and therapeutic target in PCa.
| S-EPMC7377862 | biostudies-literature
Project description:Breast cancer (BC) is one of the most fatal diseases among women all over the world. Non-coding RNAs including circular RNAs (circRNAs) have been reported to be involved in different aspects during tumorigenesis and progression. In this study, we aimed to explore the biological functions and underlying mechanism of circRPPH1 in BC. Candidate circRNAs were screened in dataset GSE101123 from Gene Expression Omnibus (GEO) database and a differentially expressed circRNA, circRPPH1, was discovered in BC. CircRPPH1 expression was higher in the cancerous tissue compared to paired adjacent tissue. Further in vitro and in vivo experiments indicated that circRPPH1 acted as an oncogene in BC. In addition, circRPPH1 was mainly localized in cytoplasm and played the role of miR-512-5p sponge. By sequestering miR-512-5p from the 3'-UTR of STAT1, circRPPH1 inhibited the suppressive role of miR-512-5p, stabilized STAT1 mRNA in BC and finally affected BC progression. In conclusion, these findings indicated that circRPPH1 acted as an oncogene and regulated BC progression via circRPPH1-miR-512-5p-STAT1 axis, which might provide a potential therapeutic target for BC treatment.
| S-EPMC8648777 | biostudies-literature