Abstract：
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.
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.
摘要：
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。
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。
