Dataset Information

Circular RNA GLIS2 promotes colorectal cancer cell motility via activation of the NF-?B pathway.

ABSTRACT: Circular RNAs (circRNAs) are a newly discovered type of biological molecule that belongs to the noncoding RNA family. Abundant evidence has shown that circRNAs are involved in the progression of various cancers. However, the particular functions of circRNAs in colorectal cancer (CRC) remain elusive. In this study, we investigated the differentially expressed circRNAs in three pairs of cancer tissue and adjacent normal tissue of CRC. We revealed that circGLIS2 expression was higher in CRC tissue and cell lines. Gain-and-loss function assays showed that circGLIS2 was involved in the regulation of cell migration. Moreover, overexpressing circGLIS2 in CRC cells activated the NF-?B pathway and induced pro-inflammatory chemokine production, which evoked tumor-associated inflammation through recruiting leukocytes. In turn, when the cancer cells were exposed to the supernatant of circGLIS2 overexpressed cancer cells, they were endowed with the ability of migration and chemokines production. Furthermore, the rescue assay confirmed that circGLIS2 activated NF-?B signaling and promoted cell migration by sponging miR-671. Overall, our study reveals that circGLIS2, acting as a potential oncogene, maintains the abnormal activation state of the NF-?B signaling pathway via the miR-671 sponge mechanism in CRC cells. This study provides a scientific basis for targeting circGLIS2 in colorectal cancer interventions.

SUBMITTER: Chen J

PROVIDER: S-EPMC7511409 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Circular RNA GLIS2 promotes colorectal cancer cell motility via activation of the NF-κB pathway.

Chen Junxiong J Yang Xiangling X Liu Ruixian R Wen Chuangyu C Wang Huihui H Huang Lanlan L Li Weiqian W Zhu Zefeng Z Zhu Yonglin Y Liu Huanliang H

Cell death & disease 20200923 9

Circular RNAs (circRNAs) are a newly discovered type of biological molecule that belongs to the noncoding RNA family. Abundant evidence has shown that circRNAs are involved in the progression of various cancers. However, the particular functions of circRNAs in colorectal cancer (CRC) remain elusive. In this study, we investigated the differentially expressed circRNAs in three pairs of cancer tissue and adjacent normal tissue of CRC. We revealed that circGLIS2 expression was higher in CRC tissue ...[more]

PMID: 32968054

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Project description:Colorectal cancer (CRC) is a common malignancy globally. The aim of the present study was to explore the role and the working mechanism of circular RNA NADPH oxidase 4 (circNOX4; circBase ID, hsa_circ_0023990) in CRC. Reverse transcription‑quantitative (RT‑q)PCR was used to examine the expression of circNOX4, NOX4 mRNA and microRNA (miR)‑485‑5p in CRC tissues and cell lines. 3‑(4,5‑Dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide and Transwell assays were performed to analyze CRC cell viability and motility. The glycolytic ability of CRC cells was assessed by measuring glucose consumption, lactate production, extracellular acidification and O2 consumption rates using commercial kits. The starBase database was used to predict the targets of circNOX4 and miR‑485‑5p, and the interaction was confirmed by dual‑luciferase reporter and RNA immunoprecipitation assays. A murine xenograft model was established to verify the role of circNOX4 in CRC in vivo. The results demonstrated that the expression of circNOX4 was upregulated in CRC tissues and cell lines compared with that in adjacent normal tissues and a normal colon epithelial cell line, respectively. The expression of circNOX4 was negatively associated with the prognosis of patients with CRC. CircNOX4 silencing suppressed the proliferation, migration, invasion and glycolysis of CRC cells. miR‑485‑5p was identified as a target of circNOX4. CircNOX4 promoted CRC progression by sponging miR‑485‑5p. miR‑485‑5p was demonstrated to bind to the 3' untranslated region (UTR) of CDC28 protein kinase regulatory subunit 1B (CKS1B). miR‑485‑5p overexpression‑mediated malignant properties of CRC cells were partly reversed by the transfection with the CKS1B overexpression plasmid. CircNOX4 silencing restrained the CRC xenograft growth in vivo. Collectively, the results of the present study demonstrated that circNOX4 may serve an oncogenic role in CRC by promoting the proliferation, migration, invasion and glycolysis of CRC cells via the miR‑485‑5p/CKS1B axis.

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.

Dataset Information

Circular RNA GLIS2 promotes colorectal cancer cell motility via activation of the NF-?B pathway.

Publications

Circular RNA GLIS2 promotes colorectal cancer cell motility via activation of the NF-κB pathway.

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