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Updated: Dec 17, 2025

Author Spotlight: RNA FISH for Locating lncRNA-SNHG6 in Osteosarcoma Cells
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Author Spotlight: RNA FISH for Locating lncRNA-SNHG6 in Osteosarcoma Cells

Published on: June 16, 2023

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Small Nucleolar RNAs Determine Resistance to Doxorubicin in Human Osteosarcoma

Martina Godel1, Deborah Morena1, Preeta Ananthanarayanan1

  • 1Department of Oncology, University of Torino, 1026 Torino, Italy.

International Journal of Molecular Sciences
|July 1, 2020
PubMed

Insights

Small nucleolar RNAs (snoRNAs) promote doxorubicin resistance in osteosarcoma. Targeting snoRNAs may offer new therapeutic strategies for chemoresistant osteosarcoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Doxorubicin (Dox) is a key chemotherapy for osteosarcoma.
  • Mechanisms of Dox resistance in osteosarcoma are not fully understood.
  • Small nucleolar RNAs (snoRNAs) are increasingly recognized for their roles in cancer.

Purpose of the Study:

  • To identify novel markers associated with Dox resistance in osteosarcoma.
  • To investigate the role of snoRNAs in Dox resistance.
  • To explore potential therapeutic targets for chemoresistant osteosarcoma.

Main Methods:

  • RT-PCR to validate snoRNA expression.
  • Overexpression of specific snoRNAs in Dox-sensitive osteosarcoma cells.
  • Assessment of Dox cytotoxicity and gene expression changes via PCR arrays.
  • Gene silencing and overexpression experiments to validate findings.

Main Results:

  • Global upregulation of snoRNAs observed in Dox-resistant osteosarcoma cells.
  • Overexpression of SNORD3A, SNORA13, and SNORA28 reduced Dox-induced cytotoxicity.
  • Upregulation of GADD45A and MYC, and downregulation of TOP2A observed in resistant cells and cells with overexpressed snoRNAs.
  • Silencing GADD45A/MYC or overexpressing TOP2A counteracted snoRNA-induced Dox resistance.

Conclusions:

  • snoRNAs induce Dox resistance in human osteosarcoma by modulating genes involved in DNA damage response, DNA repair, ribosome biogenesis, and proliferation.
  • This study establishes snoRNAs as a novel mechanism of Dox resistance in osteosarcoma.
  • Targeting snoRNAs or their downstream effectors presents a promising therapeutic avenue for chemoresistant osteosarcoma.
Keywords:
chemoresistancedoxorubicinosteosarcomasmall nucleolar RNAs

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