Basic Information
Regular Relationship :
Phenotype/DiseaseSpecieAcute Myeloid Leukemia
CeRNA1XIST[LncRNA]
miRNAmiR-29a[miRNA]
CeRNA2MYC[mRNA]
Tissue/Cell lineAML KG-1 cells
SpecieHomo sapiens (human)
CitationMol Med. 2020 Nov 24;26(1):114. doi: 10.1186/s10020-020-00229-4.
Reference title
Silencing long non-coding RNA XIST suppresses drug resistance in acute myeloid leukemia through down-regulation of MYC by elevating microRNA-29a expression.
Experimental verification
qPCR;RT-qPCR;RIP assay;Western blot;Luciferase reporter assay;
Functional description
BACKGROUND: Long non-coding RNAs (lncRNAs) are biomarkers participating in multiple disease development including acute myeloid leukemia (AML). Here, we investigated molecular mechanism of X Inactive-Specific Transcript (XIST) in regulating cellular viability, apoptosis and drug resistance in AML. METHODS: XIST, miR-29a and myelocytomatosis oncogene (MYC) expression in AML bone marrow cells collected from 62 patients was evaluated by RT-qPCR and Western blot analysis. Besides, the relationship among XIST, miR-29a and MYC was analyzed by dual luciferase reporter assay, RIP, and RNA pull down assays. AML KG-1 cells were treated with anti-tumor drug Adriamycin. The role of XIST/miR-29a/MYC in cellular viability, apoptosis and drug resistance in AML was accessed via gain- and loss-of-function approaches. At last, we evaluated role of XIST/miR-29a/MYC on tumorigenesis in vivo. RESULTS: XIST and MYC were up-regulated, and miR-29a was down-regulated in AML bone marrow cells. Silencing XIST inhibited cellular activity and drug resistance but promoted cellular apoptosis of KG-1 cells by down-regulating MYC. XIST inhibited miR-29a expression to up-regulate MYC. Moreover, silencing XIST inhibited tumorigenesis of AML cells in vivo. CONCLUSIONS: Overall, down-regulation of XIST decreased MYC expression through releasing the inhibition on miR-29a, thereby reducing drug resistance, inhibiting viability and promoting apoptosis of AML cells.
Annotations
External Annotation for XIST |
|
|---|---|
 |
LncRNA-associated competing triplets and functions. |
 |
Comprehensive experimentally supported associations between lncRNA and human cancer. |
 |
Infer genomic variations that disturb lncRNA-associated ceRNA regulation.. |
 |
Provide and annotate disease or phenotype-associated variants in human long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) or their regulatory elements. |
 |
Providing cellular-specific lncRNA-associated ceRNA networks predicted via high-throughput analysis of single-cell genomic data. |
 |
Information on all annotated and predicted human genes. |
 |
Gene nomenclature, gene families and associated resources (genomic, proteomic, phenotypic information). |
 |
Genome browser for vertebrate genomes. |
 |
An annotated collection of all publicly available DNA sequences. |
 |
A wiki-based platform for community curation of human long non-coding RNAs. |
 |
An integrated knowledge database dedicated to non-coding RNAs. |
 |
An integrated database of human annotated lncRNA transcripts. |
 |
Comprehensive annotations of eukaryotic long non-coding RNAs. |
 |
Comprehensive experimentally supported associations between lncRNA and human cancer. |
 |
A comprehensive, authoritative compendium of human genes and genetic phenotypes. |
 |
The catalogue of somatic mutations in cancer. |
