Long non-coding RNA MSC-AS1 confers imatinib resistance of gastrointestinal stromal tumor cells by activating FNDC1

Lin Chen1, Yongjian Gao1, Huaixi Yang1

  • 1Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, No. 126 Sendai Street, Nanguan District, Changchun, 130031, China.

Human Cell
|January 3, 2025
PubMed

Insights

This study identifies MSC-AS1 as a key long non-coding RNA driving imatinib resistance in gastrointestinal stromal tumors (GIST). Suppressing MSC-AS1 may offer a new strategy to overcome drug resistance in GIST patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Imatinib resistance poses a significant challenge in treating gastrointestinal stromal tumors (GIST).
  • Long non-coding RNAs (LncRNAs) are emerging as critical regulators in chemotherapy resistance.
  • Understanding the molecular mechanisms of imatinib resistance in GIST is crucial for developing effective therapies.

Purpose of the Study:

  • To identify key long non-coding RNAs (lncRNAs) involved in imatinib resistance in GIST.
  • To elucidate the functional role and underlying mechanism of MSC-AS1 in GIST imatinib resistance.

Main Methods:

  • Analysis of lncRNA expression in imatinib-resistant GIST tissues and cells.
  • In vitro cellular experiments assessing cell survival, colony formation, migration, and invasion upon MSC-AS1 modulation.
  • Investigation of the molecular mechanism involving miR-200b-3p, FNDC1, Anillin, and the PI3K-AKT signaling pathway.
  • In vivo validation of MSC-AS1's role in imatinib resistance.

Main Results:

  • MSC-AS1 was found to be significantly upregulated in imatinib-resistant GIST.
  • Overexpression of MSC-AS1 reduced GIST cell sensitivity to imatinib, enhancing cell survival, proliferation, migration, and invasion.
  • Suppression of MSC-AS1 reversed imatinib resistance in GIST cells.
  • MSC-AS1 acts by sponging miR-200b-3p, leading to upregulation of FNDC1 and Anillin, and activation of the PI3K-AKT pathway.

Conclusions:

  • MSC-AS1 plays a critical role in mediating imatinib resistance in GIST.
  • The MSC-AS1/miR-200b-3p/FNDC1/Anillin axis and PI3K-AKT pathway activation are key mechanisms driving this resistance.
  • Targeting MSC-AS1 presents a potential therapeutic strategy to overcome imatinib resistance in GIST.

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