Highly enriched exosomal lncRNA OIP5-AS1 regulates gastrointestinal stromal tumor (GIST) resistance to sunitinib through miR-145 and SOX9
Targeted therapy-induced resistance is a significant factor contributing to treatment failure in patients with gastrointestinal stromal tumors (GIST). Despite the identification of the long non-coding RNA (lncRNA) OIP5-AS1 as a critical player in human malignancy development, its role in GIST-relate...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
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| Series: | Cancer Biology & Therapy |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/15384047.2025.2522543 |
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| Summary: | Targeted therapy-induced resistance is a significant factor contributing to treatment failure in patients with gastrointestinal stromal tumors (GIST). Despite the identification of the long non-coding RNA (lncRNA) OIP5-AS1 as a critical player in human malignancy development, its role in GIST-related drug resistance remains largely unexplored. This study revealed substantial up-regulation of both OIP5-AS1 and SOX9, alongside significant down-regulation of miR-145, within sunitinib-resistant GIST cells. OIP5-AS1 emerged as a competing endogenous RNA, exerting inhibition on miR-145 while concurrently promoting the expression of SOX9. Exosome-mediated transfer of OIP5-AS1 induced heightened proliferation and invasion of GIST cells, culminating in the induction of chemoresistance to sunitinib through the miR-145/SOX9 axis. The knockdown of OIP5-AS1-expressing exosomes resulted in reduced cell proliferation and invasion in chemo-resistant GIST cells. In summary, these findings collectively suggest that OIP5-AS1 fosters GIST cell proliferation and invasion by suppressing miR-145 and up-regulating SOX9, ultimately contributing to drug resistance and tumor progression in GIST. |
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| ISSN: | 1538-4047 1555-8576 |