LAMTOR5-AS1

  • 文章类型: Journal Article
    背景:骨肉瘤(OS)耐药性通常导致预后不良。最近的证据表明,长链非编码RNA在调节肿瘤耐药性中起着至关重要的作用。
    方法:本研究旨在研究lncRNALAMTOR5-AS1在OS中的参与。进行RNA-seq和qRT-PCR,以及LAMTOR5-AS1、miR-34a-3p、使用双荧光素酶报告基因测定和RNA免疫沉淀测定来测定SIRT1和HNF4A。使用CCK-8,细胞增殖,和集落形成测定。
    结果:该研究发现,失调的LAMTOR5-AS1充当竞争性内源性RNA(ceRNA),并竞争性地保护HNF4AmRNA3'UTR免受miR-34a-3p的侵害。此外,体外功能研究表明,HNF4A可以与SIRT1物理相互作用,协同抑制骨肉瘤的耐药性。研究发现LAMTOR5-AS1通过miR-34a-3p/HNF4A或miR-34a-3p/SIRT1/HNF4A轴调节骨肉瘤耐药。
    结论:这些发现为lncRNA介导的癌症耐药性提供了新的见解,并可能作为癌症治疗的潜在生物标志物。
    BACKGROUND: Osteosarcoma (OS) drug resistance often leads to a poor prognosis. Recent evidence suggests that long non-coding RNAs play a crucial role in regulating tumor drug resistance.
    METHODS: This study aims to investigate the involvement of lncRNA LAMTOR5-AS1 in OS. RNA-seq and qRT-PCR were performed, and the relationship between LAMTOR5- AS1, miR-34a-3p, SIRT1, and HNF4A was determined using Dual-luciferase reporter assays and RNA immunoprecipitation assays. Gain- and loss-of-function assays were measured using CCK-8, cell proliferation, and colony formation assays.
    RESULTS: The study found that the dysregulated LAMTOR5-AS1 acts as a competing endogenous RNA (ceRNA) and competitively protects the HNF4A mRNA 3\' UTR from miR-34a-3p. In addition, in vitro functional studies showed that HNF4A can physically interact with SIRT1 to synergistically inhibit osteosarcoma drug resistance. The study found that LAMTOR5-AS1 regulates drug resistance in osteosarcoma through the miR-34a-3p/HNF4A or miR-34a-3p/SIRT1/HNF4A axis.
    CONCLUSIONS: These findings offer new insights into lncRNA-mediated drug resistance in cancer and may serve as potential biomarkers for cancer therapy.
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  • 文章类型: Journal Article
    BACKGROUND: Strong evidence indicated that high expression of HBXIP (also known as LAMTOR5) promotes cancer cells proliferation and helps cancer progression. Long non-coding RNAs (lncRNA) have also a crucial role in developing cancer. In this study, we aimed to determine the expression of LAMTOR5 and its nearby lncRNA, LAMTOR5-AS1 and investigate their potential as a biomarker in colorectal cancer (CRC) patients.
    METHODS: 75 tissues of colorectal tumors and non-tumor adjacent normal sampled in this study. After RNA procedure then RT-qPCR was applied for expression analysis. Moreover, in silico investigation also enrolled for predicting sponging effect of lncRNA with miRNAs.
    RESULTS: LAMTOR5 transcription level significantly overexpressed (p value < 0.001) and has shown a diagnostic potential (AUC = 0.8) in CRC. LAMTOR5-AS1 did not indicate any remarkable expression change overall, but showed a significant overexpressed in elderly patients (> 60) with CRC (p value < 0.0097). Moreover, the correlation analysis between LAMTOR5 and LAMTOR5-AS1 revealed a significant association in CRC (p value = 0.0074) which can be partly explained by its predicting act as a mediator with sponging effect on hsa-miR-let-7b-3p and hsa-miR-20a-5p.
    CONCLUSIONS: LAMTOR5 gene can be considered as prognostic biomarker for CRC. LAMTOR5-AS5 which is a nearby lncRNA of this gene could play a regulatory impact through its sponging effect on hsa-miR-let-7b-3p and hsa-miR-20a-5p which both have shown a significant impact on overall survival rate in CRC patients in high expression levels.
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