4/12/2023 0 Comments Www panfu com brThen, the correlation between DIO3OS expression and CpG456 methylation status in TCGA NSCLC samples was calculated. Seventeen methylation probes located on DIO3OS promoter and CpG456 with methylation data were retrieved from TCGA Illumina Infinium Human DNA Methylation 450k BeadChip data using the online tool UCSC Xena ( ). Thus, we next determined whether low expression of DIO3OS is correlated with methylation of CpG456. Intriguingly, the DIO3OS promoter is located on a CpG island, CpG456 ( Figure 2A). Thus, these data collectively demonstrated that DIO3OS was downregulated in NSCLC, and its low expression was related to disease progress and poor prognosis. Kaplan-Meier analysis revealed that low expression of DIO3OS was related to worse overall survival ( Figure 1E). Correlation analyses of DIO3OS expression and clinicopathological features revealed that low expression of DIO3OS was related to local invasion, lymphatic metastasis, and advanced Tumor, Node, Metastasis (TNM) stage ( Table 1). Quantitative real-time polymerase chain reaction (PCR) results showed that DIO3OS was remarkably downregulated in NSCLC tissues compared to normal tissues ( Figure 1D). To further validate the clinical relevance of DIO3OS in NSCLC, we collected 78 pairs of NSCLC tissues and matched adjacent normal lung tissues. Additionally, TCGA dataset also revealed that low expression of DIO3OS was related to shorter overall survival ( Figure 1C), analyzed by Kaplan-Meier Plotter ( ). Among these lncRNAs, we noted DIO3OS, which was not only significantly downregulated in LUAD ( Figure 1A) but also significantly downregulated in LUSC ( Figure 1B). The 100 most significantly downregulated lncRNAs were shown in Table S1. To search the lncRNAs differently expressed in NSCLC, we analyzed TCGA dataset using the online tool Gene Expression Profiling Interactive Analysis (GEPIA) ( ). In conclusion, these findings identified DIO3OS as an important protective factor against NSCLC via modulating hnRNPK-MYC-CDC25A axis. Additionally, depletion of hnRNPK blocked the tumor-suppressive roles of DIO3OS in NSCLC. DIO3OS competitively bound heterogeneous nuclear ribonucleoprotein K (hnRNPK), repressed the binding of hnRNPK to MYC DNA and MYC mRNA, reduced the promoting roles of hnRNPK on MYC transcription and translation, led to the repression of MYC transcription and translation, and therefore remarkably decreased the expression of MYC and CDC25A, a downstream target of MYC. DIO3OS knockdown exhibited opposite biological effects. DIO3OS also repressed NSCLC tumorigenesis and metastasis in vivo. Ectopic expression of DIO3OS repressed NSCLC cell growth and motility and promoted NSCLC cell apoptosis in vitro. DIO3OS is downregulated in NSCLC, and its low expression is related to poor prognosis. In this study, we identified a DNA-methylation-repressed lncRNA DIO3 opposite strand upstream RNA (DIO3OS) in NSCLC. However, the contributions of lncRNAs to DNA-methylation-induced oncogenic effects in NSCLC remain largely unknown. Recently, long non-coding RNAs (lncRNAs) were revealed to be implicated in a variety of malignancies, including non-small cell lung cancer (NSCLC). DNA methylation is a class of epigenetic modification manner, which is responsible for the inactivation of various tumor suppressors.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |