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Updated: Jun 4, 2025

Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
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.
Abstract:
Imatinib resistance is a major obstacle to the successful treatment of gastrointestinal stromal tumors (GIST). Long non-coding RNAs (LncRNAs) have been identified as important regulatory factors in chemotherapy resistance. This study aimed to identify key lncRNAs involved in imatinib resistance of GISTs. First, MSC-AS1 was found to be upregulated in imatinib-resistant GIST tissues and imatinib-resistant GIST cells. Cellular experiments demonstrated that MSC-AS1 overexpression decreased imatinib sensitivity of GIST cells, evidenced by increased cell survival, colony formation, migration, and invasion. Moreover, suppression of MSC-AS1 improved the imatinib resistance of imatinib-resistant GIST cells. Furthermore, MSC-AS1 upregulated the expression of FNDC1 and Anillin via sponging miR-200b-3p, activated the phosphatidylinositol-3-kinase-AKT signaling pathway, and thereby driving imatinib resistance in vitro and in vivo. Overall, this study elucidates the crucial role and mechanism of MSC-AS1 in the imatinib resistance of GIST, providing the potential therapeutic strategy for overcoming the imatinib resistance of GIST.
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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