LAMTOR5-AS1 Regulates Chemotherapy-induced Oxidative Stress via the miR-34a-3p/SIRT1/HNF4A Axis in Osteosarcoma Cells.

IF 3.5 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Current medicinal chemistry Pub Date : 2024-07-11 DOI:10.2174/0109298673316534240708111058

Fangfang Zhao, Chao Wei, Youguang Pu, Chunbao Zang

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Abstract

Introduction: 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.

Method: 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.

Result: 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.

Conclusion: 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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LAMTOR5-AS1 通过 miR-34a-3p/SIRT1/HNF4A 轴调节骨肉瘤细胞中化疗诱导的氧化应激

导言：骨肉瘤（Osteosarcoma，OS）的耐药性通常会导致不良预后。最近的证据表明，长非编码RNA在调控肿瘤耐药性方面发挥着重要作用：本研究旨在探讨lncRNA LAMTOR5-AS1在OS中的参与。研究采用RNA-seq和qRT-PCR技术，并利用双荧光素酶报告实验和RNA免疫沉淀实验确定LAMTOR5-AS1、miR-34a-3p、SIRT1和HNF4A之间的关系。利用 CCK-8、细胞增殖和集落形成试验对功能增益和功能缺失进行了测定：研究发现，失调的 LAMTOR5-AS1 可作为竞争性内源性 RNA（ceRNA），竞争性地保护 HNF4A mRNA 3' UTR 免受 miR-34a-3p 的影响。此外，体外功能研究表明，HNF4A 可与 SIRT1 发生物理相互作用，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轴调节骨肉瘤的耐药性：这些发现为了解 lncRNA 介导的癌症耐药性提供了新的视角，可作为癌症治疗的潜在生物标记物。

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来源期刊

Current medicinal chemistry 医学-生化与分子生物学

CiteScore

8.60

自引率

2.40%

发文量

468

审稿时长

3 months

期刊介绍： Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.