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LAMTOR5-AS1通过miR-34a-3p/SIRT1/HNF4A轴调控骨肉瘤细胞中化疗诱导的氧化应激。

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

作者信息

Zhao Fangfang, Wei Chao, Pu Youguang, Zang Chunbao

机构信息

Department of Cancer Epigenetics Program, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China.

Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China.

出版信息

Curr Med Chem. 2024 Jul 11. doi: 10.2174/0109298673316534240708111058.

DOI:10.2174/0109298673316534240708111058

PMID:38994619

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.

摘要

引言

骨肉瘤（OS）耐药常导致预后不良。最近的证据表明，长链非编码RNA在调节肿瘤耐药中起关键作用。

方法

本研究旨在探讨lncRNA LAMTOR5-AS1在骨肉瘤中的作用。进行了RNA测序和qRT-PCR，并使用双荧光素酶报告基因检测和RNA免疫沉淀检测确定了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检测进行功能获得和功能缺失检测。

结果

研究发现，失调的LAMTOR5-AS1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，协同抑制骨肉瘤耐药。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。