Highly enriched exosomal lncRNA OIP5-AS1 regulates gastrointestinal stromal tumor (GIST) resistance to sunitinib

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Cui-Hua Wang1, Xin-Ming Yao1, Chun-Xia Pan2

  • 1Oncology Department, Shanghai Putuo District Liqun Hospital, Shanghai, China.

Cancer Biology & Therapy
|June 23, 2025
PubMed

Insights

Long non-coding RNA OIP5-AS1 promotes gastrointestinal stromal tumor (GIST) progression and sunitinib resistance by regulating the miR-145/SOX9 axis. Targeting OIP5-AS1 may overcome drug resistance in GIST.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Drug resistance is a major challenge in treating gastrointestinal stromal tumors (GIST).
  • The role of long non-coding RNA (lncRNA) OIP5-AS1 in GIST drug resistance is not well understood.
  • OIP5-AS1 is implicated in various human cancers.

Purpose of the Study:

  • To investigate the role of OIP5-AS1 in sunitinib resistance in GIST.
  • To elucidate the molecular mechanism underlying OIP5-AS1-mediated drug resistance.
  • To explore OIP5-AS1 as a potential therapeutic target in GIST.

Main Methods:

  • Analysis of OIP5-AS1, SOX9, and miR-145 expression in sunitinib-resistant GIST cells.
  • Investigation of OIP5-AS1 as a competing endogenous RNA (ceRNA) for miR-145.
  • Assessment of exosome-mediated transfer of OIP5-AS1.
  • Evaluation of OIP5-AS1 knockdown effects on GIST cell behavior and drug resistance.

Main Results:

  • OIP5-AS1 and SOX9 were upregulated, while miR-145 was downregulated in sunitinib-resistant GIST cells.
  • OIP5-AS1 acts as a ceRNA, inhibiting miR-145 and promoting SOX9 expression.
  • Exosomal OIP5-AS1 transfer enhanced GIST cell proliferation, invasion, and sunitinib resistance via the miR-145/SOX9 axis.
  • Knockdown of OIP5-AS1 in exosomes reduced proliferation and invasion in chemo-resistant GIST cells.

Conclusions:

  • OIP5-AS1 promotes GIST cell proliferation and invasion by suppressing miR-145 and upregulating SOX9.
  • OIP5-AS1 contributes to sunitinib resistance and tumor progression in GIST.
  • Targeting OIP5-AS1 or its exosomal transfer presents a potential strategy to overcome drug resistance in GIST.
Keywords:
Gastrointestinal stromal tumorbiomarkerdrug resistanceexosomelncRNA

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