Basic Information
Regular Relationship :
Phenotype/DiseaseSpecieRenal Cancer
CeRNA1TRAF3IP2-AS1[LncRNA]
miRNAmiR-200a-3p[miRNA]
CeRNA2PTEN[mRNA]
Tissue/Cell linetRCC tissues and cells
SpecieHomo sapiens (human)
CitationJ Hematol Oncol. 2021 Mar 19;14(1):46. doi: 10.1186/s13045-021-01059-5.
Reference title
Low expression of TRAF3IP2-AS1 promotes progression of NONO-TFE3 translocation renal cell carcinoma by stimulating N(6)-methyladenosine of PARP1 mRNA and downregulating PTEN.
Experimental verification
FISH;qRT-PCR;RNA immunoprecipitation;Western blot;FISH;Immunohistochemistry;luciferase assay;RNA immunoprecipitation;
Functional description
BACKGROUND: NONO-TFE3 translocation renal cell carcinoma (NONO-TFE3 tRCC) is one subtype of RCCs associated with Xp11.2 translocation/TFE3 gene fusions RCC (Xp11.2 tRCCs). Long non-coding RNA (lncRNA) has attracted great attention in cancer research. The function and mechanisms of TRAF3IP2 antisense RNA 1 (TRAF3IP2-AS1), a natural antisense lncRNA, in NONO-TFE3 tRCC remain poorly understood. METHODS: FISH and qRT-PCR were undertaken to study the expression, localization and clinical significance of TRAF3IP2-AS1 in Xp11.2 tRCC tissues and cells. The functions of TRAF3IP2-AS1 in tRCC were investigated by proliferation analysis, EdU staining, colony and sphere formation assay, Transwell assay and apoptosis analysis. The regulatory mechanisms among TRAF3IP2-AS1, PARP1, PTEN and miR-200a-3p/153-3p/141-3p were investigated by luciferase assay, RNA immunoprecipitation, Western blot and immunohistochemistry. RESULTS: The expression of TRAF3IP2-AS1 was suppressed by NONO-TFE3 fusion in NONO-TFE3 tRCC tissues and cells. Overexpression of TRAF3IP2-AS1 inhibited the proliferation, migration and invasion of UOK109 cells which were derived from cancer tissue of patient with NONO-TFE3 tRCC. Mechanistic studies revealed that TRAF3IP2-AS1 accelerated the decay of PARP1 mRNA by direct binding and recruitment of N(6)-methyladenosie methyltransferase complex. Meanwhile, TRAF3IP2-AS1 competitively bound to miR-200a-3p/153-3p/141-3p and prevented those from decreasing the level of PTEN. CONCLUSIONS: TRAF3IP2-AS1 functions as a tumor suppressor in NONO-TFE3 tRCC progression and may serve as a novel target for NONO-TFE3 tRCC therapy. TRAF3IP2-AS1 expression has the potential to serve as a novel diagnostic and prognostic biomarker for NONO-TFE3 tRCC detection.
Annotations
External Annotation for TRAF3IP2-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. |
