骨肉瘤（OS）耐药性常常导致预后不良。最近的证据表明长链非编码RNA在调节肿瘤耐药性中发挥着至关重要的作用。本研究旨在探讨lncRNA LAMTOR5-AS1在OS中的参与。进行了 RNA-seq 和 qRT-PCR，并使用双荧光素酶报告基因测定和 RNA 免疫沉淀测定确定了 LAMTOR5-AS1、miR-34a-3p、SIRT1 和 HNF4A 之间的关系。使用 CCK-8、细胞增殖和集落形成测定来测量功能获得和丧失的测定。研究发现失调的 LAMTOR5-AS1 作为竞争性内源 RNA (ceRNA) 并竞争性保护 HNF4A mRNA 3'来自 miR-34a-3p 的 UTR。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轴调节骨肉瘤的耐药性。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。版权所有© Bentham Science Publishers；如有任何疑问，请发送电子邮件至 epub@benthamscience.net。

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.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.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.These findings offer new insights into lncRNA-mediated drug resistance in cancer and may serve as potential biomarkers for cancer therapy.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.