%0 Journal Article
%T LAMTOR5-AS1 Regulates Chemotherapy-induced Oxidative Stress via the miR-34a-3p/SIRT1/HNF4A Axis in Osteosarcoma Cells.
%A Zhao F
%A Wei C
%A Pu Y
%A Zang C
%J Curr Med Chem
%V 0
%N 0
%D 2024 Jul 11
%M 38994619
%F 4.74
%R 10.2174/0109298673316534240708111058
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>These findings offer new insights into lncRNA-mediated drug resistance in cancer and may serve as potential biomarkers for cancer therapy.