Basic Information
Regular Relationship :
Phenotype/DiseaseSpecieGastric Cancer
CeRNA1RP11-874J12.4[LncRNA]
miRNAmiR-3972[miRNA]
CeRNA2SSR2[mRNA]
Tissue/Cell lineMkn-45 And Ags Cells
SpecieHomo sapiens (human)
CitationAm J Transl Res. 2021 Jun 15;13(6):5892-5910. eCollection 2021.
Reference title
RP11-874J12.4, a novel lncRNA, confers chemoresistance in human gastric cancer cells by sponging miR-3972 and upregulating SSR2 expression.
Experimental verification
qRT-PCR
Functional description
Increasing evidence has revealed the contributions of long noncoding RNAs (lncRNAs) in the modulation of drug resistance in gastric cancer. In the present study, we explored the role of a novel lncRNA, RP11-874J12.4, in regulating chemoresistance in gastric cancer and determined the underlying molecular mechanisms. We observed that compared with normal controls, human gastric cancer tissues and cell lines, including MKN-45 and AGS cells, expressed higher RP11-874J12.4 levels. RP11-874J12.4 knockdown sensitized MKN-45 and AGS cells to docetaxel and cisplatin in terms of cell viability and apoptosis rate. In addition, RP11-874J12.4 was found to be a competing endogenous RNA that sponged microRNA (miR)-3972, which showed significantly reduced expression in human gastric cancer tissues and cell lines. Furthermore, signal sequence receptor subunit 2 (SSR2) was identified as a downstream target of miR-3972, and the miR-3972/SSR2 axis was found to regulate chemoresistance in MKN-45 and AGS cells. SSR2 downregulation further sensitized gastric cancer cells with RP11-874J12.4 knockdown to chemotherapeutic drugs via enhanced apoptosis, which was evidenced by significantly upregulated expressions of cleaved caspase-3, cleaved caspase-9, and Bax and downregulated expression of Bcl-2. Furthermore, RP11-874J12.4 knockdown markedly inhibited the growth of xenograft MKN-45 cells in nude mice, which was associated with an increased expression of miR-3972 and decreased expression of SSR2 in tumors. Therefore, the RP11-874J12.4/miR-3972/SSR2 axis plays important roles in the regulation of chemoresistance in MKN-45 and AGS cells and may serve as a target for the diagnosis and treatment of human gastric cancer.
Annotations
External Annotation for RP11-874J12.4 |
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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. |
