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TFAP2C-mediated LINC00922 signaling underpins doxorubicin-resistant osteosarcoma

Zenghui Gu1, Yuanxi Zhou1, Chenye Cao1

  • 1Department of Orthopaedics, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|June 22, 2020
PubMed

Insights

Long noncoding RNA LINC00922 promotes doxorubicin resistance in osteosarcoma by sponging miR-424-5p. This feedback loop involving TFAP2C offers a potential therapeutic target for osteosarcoma treatment.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Long noncoding RNAs (lncRNAs) are implicated in osteosarcoma (OS) regulation.
  • The role of lncRNAs in doxorubicin (DXR)-resistant OS remains largely unknown.
  • Understanding these mechanisms is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To investigate the function of lncRNA LINC00922 in doxorubicin resistance in osteosarcoma.
  • To elucidate the molecular mechanisms underlying LINC00922's role in DXR-resistant OS.
  • To identify potential therapeutic targets for overcoming DXR resistance in OS.

Main Methods:

  • LncRNA expression profiling using microarray in DXR-resistant and parental OS cells.
  • Luciferase reporter assays and chromatin immunoprecipitation to determine molecular interactions.
  • Cell Counting Kit-8 (CCK-8) assay to evaluate DXR sensitivity and tumor growth.

Main Results:

  • LINC00922 was significantly upregulated in OS tissues and DXR-resistant cells.
  • LINC00922 overexpression increased DXR IC50, while its knockdown repressed OS cell growth.
  • LINC00922 functioned as a sponge for miR-424-5p, which targets TFAP2C mRNA.

Conclusions:

  • A positive feedback loop involving TFAP2C, LINC00922, and miR-424-5p was identified.
  • This TFAP2C/LINC00922/miR-424-5p feedback loop plays a critical role in DXR resistance in OS.
  • The findings suggest novel therapeutic strategies targeting this feedback loop for OS treatment.
Keywords:
Doxorubicin-resistanceLINC00922OsteosarcomaTFAP2C

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