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Long noncoding RNA SNHG12 mediates doxorubicin resistance of osteosarcoma via miR-320a/MCL1 axis

Binghua Zhou1, Lijun Li2, Yajing Li3

  • 1Department of Spinal Surgery, Affiliated Longhua Central Hospital, Guangdong Medical University, Shenzhen 518110, Guangdong, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|August 19, 2018
PubMed

Insights

High expression of small nucleolar RNA host gene 12 (SNHG12) promotes doxorubicin resistance in osteosarcoma by inhibiting miR-320a, which targets MCL1. This finding offers a potential therapeutic target for overcoming drug resistance in osteosarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Long non-coding RNA SNHG12 is overexpressed in various cancers and linked to multidrug resistance.
  • The specific role of SNHG12 in doxorubicin resistance in osteosarcoma remains largely uncharacterized.

Purpose of the Study:

  • To investigate the function and molecular mechanism of SNHG12 in doxorubicin resistance in osteosarcoma.
  • To explore the potential of targeting the SNHG12/miR-320a/MCL1 axis for therapeutic intervention.

Main Methods:

  • Analysis of SNHG12 expression in osteosarcoma tissues and cell lines.
  • Dual luciferase reporter assays and RNA immunoprecipitation to confirm the interaction between SNHG12 and miR-320a.
  • Assessment of doxorubicin sensitivity following SNHG12 knockdown and miR-320a mimic transfection.

Main Results:

  • High SNHG12 expression correlated with doxorubicin resistance and poor survival in osteosarcoma patients.
  • Doxorubicin-resistant osteosarcoma cells exhibited significantly higher SNHG12 levels.
  • SNHG12 directly targeted miR-320a, and its knockdown led to miR-320a upregulation and increased doxorubicin sensitivity.
  • miR-320a was found to inhibit the expression of Myeloid cell leukemia 1 (MCL1).

Conclusions:

  • SNHG12 promotes doxorubicin resistance in osteosarcoma by sponging miR-320a, thereby upregulating MCL1 expression.
  • The SNHG12/miR-320a/MCL1 axis represents a potential therapeutic target for overcoming doxorubicin resistance in osteosarcoma.
Keywords:
DoxorubicinMCL1OsteosarcomaResistanceSNHG12miR-320a

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