Basic Information
Regular Relationship :
Phenotype/DiseaseSpecieNon-Small Cell Lung Cancer
CeRNA1circ_0014130[Circular RNA]
miRNAmiR-545-3p[miRNA]
CeRNA2YAP1[mRNA]
Tissue/Cell lineNon-Small-Cell Lung Cancer Cells
SpecieHomo sapiens (human)
CitationCytotechnology. 2021 Aug;73(4):571-584. doi: 10.1007/s10616-021-00478-z. Epub 2021 May 25.
Reference title
Blocking circ_0014130 suppressed drug resistance and malignant behaviors of docetaxel resistance-acquired NSCLC cells via regulating miR-545-3p-YAP1 axis.
Experimental verification
Dual-luciferase reporter assay;MTT assay;RNA immunoprecipitation;Flow Cytometry assay;Luciferase reporter assay;RNA immunoprecipitation;MTT assay;
Functional description
Recent evidences have claimed that circular RNAs are deregulated in docetaxel (DTX) resistance in malignant tumors, including non-small-cell lung cancer (NSCLC). Hsa_circ_0014130 (circ_0014130) is a new biomarker in NSCLC. However, its role in DTX-resistant NSCLC remained to be annotated. In this study, real-time PCR was used to measure expression of circ_0014130, and circ_0014130 was upregulated in NSCLC tumors and DTX-resistant NSCLC cells (NCI-H1299/DTX and A549/DTX). MTT assay analyzed the half inhibitory concentration (IC50) of DTX, and it was lowered by circ_0014130 interference in DTX-resistant NSCLC cells. Moreover, colony formation assay, flow cytometry, transwell assays, and xenograft tumor model revealed that silencing circ_0014130 facilitated apoptosis rate of DTX-resistant NSCLC cells, suppressed the colony formation, migration and invasion, and retarded xenograft tumor growth in nude mice. Dual-luciferase reporter assay and RNA immunoprecipitation confirmed that circ_0014130 was one competing endogenous RNA (ceRNA) for miRNA (miR)-545-3p, and circ_0014130 modulated expression of yes-associated protein 1 (YAP1), a target gene for miR-545-3p. YAP1 upregulation and miR-545-3p downregulation were allied with circ_0014130 upregulation in NSCLC tumors and DTX-resistant NSCLC cells. Functionally, downregulating miR-545-3p could abate the effects of circ_0014130 knockdown in DTX-resistant NSCLC cells in vitro, whereas its overexpression exerted similar effects of circ_0014130 knockdown. Either, restoring YAP1 partially reversed miR-545-3p effects in DTX-resistant NSCLC cells. Collectively, there might be a novel circ_0014130-miR-545-3p-YAP1 ceRNA pathway in regulation of chemoresistance and malignant behaviors of DTX-resistant NSCLC cells, suggesting a potential therapeutic approach for DTX resistance.
Annotations
External Annotation for circ_0014130 |
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LncRNA-associated competing triplets and functions. |
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Comprehensive experimentally supported associations between lncRNA and human cancer. |
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Infer genomic variations that disturb lncRNA-associated ceRNA regulation.. |
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Provide and annotate disease or phenotype-associated variants in human long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) or their regulatory elements. |
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Providing cellular-specific lncRNA-associated ceRNA networks predicted via high-throughput analysis of single-cell genomic data. |
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Information on all annotated and predicted human genes. |
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Gene nomenclature, gene families and associated resources (genomic, proteomic, phenotypic information). |
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Genome browser for vertebrate genomes. |
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An annotated collection of all publicly available DNA sequences. |
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A wiki-based platform for community curation of human long non-coding RNAs. |
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An integrated knowledge database dedicated to non-coding RNAs. |
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An integrated database of human annotated lncRNA transcripts. |
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Comprehensive annotations of eukaryotic long non-coding RNAs. |
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Comprehensive experimentally supported associations between lncRNA and human cancer. |
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A comprehensive, authoritative compendium of human genes and genetic phenotypes. |
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The catalogue of somatic mutations in cancer. |
