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Has_circ_0010220 regulates the miR-574-3p/IL-6 axis to increase doxorubicin resistance in osteosarcoma

Yanglin Gu1, Guangchang Wang1, Baocai Ran2

  • 1Department of Orthopedics, The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, P.R. China.

Human & Experimental Toxicology
|October 17, 2022
PubMed
Abstract

Insights

Hsa_circ_0010220 promotes osteosarcoma (OS) drug resistance by regulating the miR-574-3p/IL-6 axis. Silencing hsa_circ_0010220 can reduce this resistance, highlighting its potential as a therapeutic biomarker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcoma (OS) is a primary bone cancer with aggressive behavior.
  • Drug resistance, particularly to chemotherapy, presents a significant challenge in OS treatment.
  • Understanding the molecular mechanisms underlying doxorubicin (DOX) resistance is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the functional role of hsa_circ_0010220 in doxorubicin (DOX) resistance in osteosarcoma (OS).
  • To elucidate the underlying molecular mechanism of hsa_circ_0010220 in mediating DOX resistance.
  • To explore the potential of hsa_circ_0010220 as a biomarker for OS treatment.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) and ELISA were used to measure hsa_circ_0010220, IL-6, and miR-574-3p levels.
  • Cell Counting Kit-8 assay determined the half-inhibitory concentration (IC50) of DOX.
  • RNA pull-down, RNA immunoprecipitation, and dual-luciferase reporter assays identified molecular interactions.

Main Results:

  • Hsa_circ_0010220 and IL-6 were upregulated, while miR-574-3p was downregulated in DOX-resistant OS tissues and cells.
  • Silencing hsa_circ_0010220 reduced in vitro DOX resistance.
  • Hsa_circ_0010220 sponges miR-574-3p, leading to increased IL-6 expression and enhanced DOX resistance.

Conclusions:

  • Hsa_circ_0010220 promotes OS resistance to DOX through the regulation of the miR-574-3p/IL-6 axis.
  • Targeting hsa_circ_0010220 offers a potential therapeutic strategy for overcoming DOX resistance in OS.
  • Hsa_circ_0010220 may serve as a promising biomarker for predicting and treating OS.
Keywords:
Hsa_circ_0010220IL-6doxorubicin resistancemiR-574-3posteosarcoma

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