LAMTOR5-AS1 Regulates Chemotherapy-induced Oxidative Stress via the miR-34a-3p/SIRT1/HNF4A Axis in Osteosarcoma Cells-Reference-Cited by-同舟云学术

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

Published:2024-07-11 Issue: Volume:31 Page:
ISSN:0929-8673
Container-title:Current Medicinal Chemistry
language:en
Short-container-title:CMC

Author:

Zhao Fangfang¹,Wei Chao²,Pu Youguang³,Zang Chunbao⁴^ORCID

Affiliation:

1. 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

2. 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

3. 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;

4. Department of Radiation Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China

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.

Publisher

Bentham Science Publishers Ltd.