Dataset Information

Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA.

ABSTRACT: The regulatory loop between long noncoding RNAs (lncRNAs) and microRNAs has a dynamic role in transcriptional and translational regulation, and is involved in cancer. However, the regulatory circuitry between lncRNAs and microRNAs in tumorigenesis remains elusive. Here we demonstrate that a nuclear lncRNA LINC00336 is upregulated in lung cancer and functions as an oncogene by acting as a competing endogenous RNA (ceRNAs). LINC00336 bound RNA-binding protein ELAVL1 (ELAV-like RNA-binding protein 1) using nucleotides 1901-2107 of LINC00336 and the RRM interaction domain and key amino acids (aa) of ELAVL1 (aa 101-213), inhibiting ferroptosis. Moreover, ELAVL1 increased LINC00336 expression by stabilizing its posttranscriptional level, whereas LSH (lymphoid-specific helicase) increased ELAVL1 expression through the p53 signaling pathway, further supporting the hypothesis that LSH promotes LINC00336 expression. Interestingly, LINC00336 served as an endogenous sponge of microRNA 6852 (MIR6852) to regulate the expression of cystathionine-?-synthase (CBS), a surrogate marker of ferroptosis. Finally, we found that MIR6852 inhibited cell growth by promoting ferroptosis. These data show that the network of lncRNA and ceRNA has an important role in tumorigenesis and ferroptosis.

SUBMITTER: Wang M

PROVIDER: S-EPMC6889193 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA.

Wang Min M Mao Chao C Ouyang Lianlian L Liu Yating Y Lai Weiwei W Liu Na N Shi Ying Y Chen Ling L Xiao Desheng D Yu Fenglei F Wang Xiang X Zhou Hu H Cao Ya Y Liu Shuang S Yan Qin Q Tao Yongguang Y Zhang Bin B

Cell death and differentiation 20190220 11

The regulatory loop between long noncoding RNAs (lncRNAs) and microRNAs has a dynamic role in transcriptional and translational regulation, and is involved in cancer. However, the regulatory circuitry between lncRNAs and microRNAs in tumorigenesis remains elusive. Here we demonstrate that a nuclear lncRNA LINC00336 is upregulated in lung cancer and functions as an oncogene by acting as a competing endogenous RNA (ceRNAs). LINC00336 bound RNA-binding protein ELAVL1 (ELAV-like RNA-binding protein ...[more]

PMID: 30787392

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Project description:PurposeThis study was aimed to develop a lncRNA-associated competing endogenous RNA (ceRNA) network to provide further understanding of the ceRNA regulatory mechanism and pathogenesis in colorectal cancer (CRC).Patients and methodsExpression profiles of mRNAs, lncRNAs, and miRNAs, and clinical information for CRC patients were obtained from The Cancer Genome Atlas. The differentially expressed mRNAs, lncRNAs, and miRNAs (referred to as "DEmRNAs", "DElncRNAs", and "DEmiRNAs", respectively) were screened out between 539 CRC samples and 11 normal samples. The interactions between DElncRNAs and DEmiRNAs were predicted by miRcode. The DEmRNAs targeted by the DEmiRNAs were retrieved according to TargetScan, miRTar-Base, and miRDB. The lncRNA-miRNA-mRNA ceRNA network was constructed based on the DEmiRNA-DElncRNA and DEmiRNA-DEmRNA interactions. Functional enrichment analysis revealed the biological processes and pathways of DEmRNAs involved in the development of CRC. Key lncRNAs were further analyzed for their associations with overall survival and clinical features of CRC patients.ResultsA total of 1,767 DEmRNAs, 608 DElncRNAs, and 283 DEmiRNAs were identified as CRC-specific RNAs. Three hundred eighty-two DEmiRNA-DElncRNA interactions and 68 DEmiRNA-DEmRNA interactions were recognized according to the relevant databases. The lncRNA-miRNA-mRNA ceRNA network was constructed using 25 DEmiRNAs, 52 DEmRNAs, and 64 DElncRNAs. Two DElncRNAs, five DEmiRNAs, and six DEmRNAs were demonstrated to be related to the prognosis of CRC patients. Four DElncRNAs were found to be associated with clinical features. Twenty-eight Gene Ontology terms and 10 Kyoto Encyclopedia of Genes and Genomes pathways were found to be significantly enriched by the DEmRNAs in the ceRNA network.ConclusionOur results showed cancer-specific mRNA, lncRNA, and miRNA expression patterns and enabled us to construct an lncRNA-associated ceRNA network that provided new insights into the molecular mechanisms of CRC. Key RNA transcripts related to the overall survival and clinical features were also found with promising potential as biomarkers for diagnosis, survival prediction, and classification of CRC.

Dataset Information

Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA.

Publications

Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA.

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