Basic Information
Regular Relationship :
Phenotype/DiseaseSpecieChronic Myelocytic Leukemia
CeRNA1NEAT1[LncRNA]
miRNAmiR-766-5p[miRNA]
CeRNA2CDKN1A[mRNA]
Tissue/Cell lineChronic Myelocytic Leukemia Cells
SpecieHomo sapiens (human)
CitationFront Oncol. 2021 Jul 20;11:679634. doi: 10.3389/fonc.2021.679634. eCollection 2021.
Reference title
m(6)A Modification of lncRNA NEAT1 Regulates Chronic Myelocytic Leukemia Progression via miR-766-5p/CDKN1A Axis.
Experimental verification
Flow cytometry assay;RNA immunoprecipitation;Western blot;Flow Cytometry assay;Luciferase reporter assay;RNA immunoprecipitation;RNA pull-down;
Functional description
BACKGROUND: Chronic myeloid leukemia (CML) is an acquired hematopoietic stem malignant disease originating from the myeloid system. Long non-coding RNAs (lncRNAs) have been widely explored in cancer tumorigenesis. However, their roles in CML remain largely unclear. METHODS: The peripheral blood mononuclear cells (PBMCs) and CML cell lines (K562, KCL22, MEG01, BV173) were collected for in vitro research. Real-time quantitative polymerase chain reaction was used to determine the mRNA expression levels. Cell viability and apoptosis were analyzed by cell counting kit 8 and flow cytometry assays. The targeting relationships were predicted using Starbase and TargetScan and ulteriorly verified by RNA pull-down and luciferase reporter assays. Western blotting assay was performed to assess the protein expressions. N6-methyladenosine (m6A) modification sites were predicted by SRAMP and confirmed by Methylated RNA immunoprecipitation (MeRIP) assay. RESULTS: LncRNA nuclear-enriched abundant transcript 1 (NEAT1) expression levels were decreased in the CML cell lines and PBMCs of CML patients. Moreover, METTL3-mediated m6A modification induced the aberrant expression of NEAT1 in CML. Overexpression of NEAT1 inhibited cell viability and promoted the apoptosis of CML cells. Additionally, miR-766-5p was upregulated in CML PBMCs and abrogated the effects of NEAT1 on cell viability and apoptosis of the CML cells. Further, CDKN1A was proved to be the target gene of miR-766-5p and was downregulated in the CML PBMCs. Knockdown of CDKN1A reversed the effects of NEAT1. CONCLUSION: The current research elucidates a novel METTL3/NEAT1/miR-766-5p/CDKN1A axis which plays a critical role in the progression of CML.
Annotations
External Annotation for NEAT1 |
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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. |
