Basic Information
Regular Relationship :
Phenotype/DiseaseSpecieGastric Cancer
CeRNA1NUTM2A-AS1[LncRNA]
miRNAmiR-376a[miRNA]
CeRNA2TET1[mRNA]
Tissue/Cell linegastric cancer cells
SpecieHomo sapiens (human)
CitationCancer Med. 2020 Dec;9(24):9499-9510. doi: 10.1002/cam4.3544. Epub 2020 Oct 22.
Reference title
LncRNA NUTM2A-AS1 positively modulates TET1 and HIF-1A to enhance gastric cancer tumorigenesis and drug resistance by sponging miR-376a.
Experimental verification
MTT assay;qPCR;RT-qPCR;RNA immunoprecipitation;Western blot;luciferase assay;RNA immunoprecipitation;MTT assay;
Functional description
Long noncoding RNA NUTM2A-AS1 has been shown to be dysregulated in non-small cell lung carcinoma. To date, it is unclear whether NUTM2A-AS1 plays a role in gastric cancer progression. The purpose of this study is to elucidate the molecular mechanism of the role of NUTM2A-AS1 in gastric cancer. mRNA and protein levels were measured by RT-qPCR and western blot methods. Invasion ability was examined by transwell assay. Cell viability was determined by MTT assay. Dual-luciferase assay, RNA pull down, and RNA immunoprecipitation were used to confirm direct binding of between miR-376a and NUTM2A-AS1 or TET1. Xenografting tumor assay and TCGA analysis showed the contributory role of NUTM2A-AS1 in vivo and human clinical setting. Our results suggested that NUTM2A-AS1 promoted cell viability, invasion, and drug resistance of gastric cancer cells, which was largely rescued by miR-376a. More interestingly, TET1 and HIF-1A were negatively regulated by miR-376a. TET1 could interact with HIF-1A to modulate PD-L1. Finally, we revealed that PD-L1 was key to NUTM2A-AS1- and miR-376a-mediated tumorigenesis and drug resistance. In summary, our conclusions facilitate us understand the underlying mechanism and develop novel treatment strategy for gastric cancer.
Annotations
External Annotation for NUTM2A-AS1 |
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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. |
