Targeting LINC02544/miR-497-5p/CAPRIN1 axis via exosome-based siRNA to overcome immunotherapy resistance in triple-negative breast cancer
Abstract Background Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression, leading to poor clinical outcomes and resistance to targeted therapies. Immunotherapy has shown limited succe...
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BMC
2025-08-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01336-w |
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| author | Bin Lian Jiayi Li Shihui Tang Ting Li Jinping Li |
| author_facet | Bin Lian Jiayi Li Shihui Tang Ting Li Jinping Li |
| author_sort | Bin Lian |
| collection | DOAJ |
| description | Abstract Background Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression, leading to poor clinical outcomes and resistance to targeted therapies. Immunotherapy has shown limited success due to the development of resistance mechanisms. This study aimed to investigate the role of long non-coding RNA LINC02544 in mediating immunotherapy resistance through regulation of the miR-497-5p/CAPRIN1 axis in TNBC. Methods Bioinformatic analyses of TCGA and GEO databases were performed to assess LINC02544 and miR-497-5p expression in TNBC tissues. In vitro experiments evaluated the regulatory effects of LINC02544 on miR-497-5p and CAPRIN1 expression, as well as TNBC cell proliferation and migration. Exosome-mediated siRNA delivery targeting LINC02544 (exo/si-LINC02544) was tested both in vitro and in vivo in combination with a PD-1 inhibitor in a TNBC mouse model. Results LINC02544 was significantly overexpressed in TNBC, while miR-497-5p was downregulated. In vitro, LINC02544 silencing via exo/si-LINC02544 reduced CAPRIN1 levels, upregulated miR-497-5p, and inhibited TNBC cell proliferation and migration. In vivo, exo/si-LINC02544 combined with PD-1 blockade suppressed tumor growth and enhanced immune cell infiltration. Conclusions Targeting the LINC02544/miR-497-5p/CAPRIN1 axis with exosome-based siRNA delivery represents a promising therapeutic strategy to overcome immunotherapy resistance in TNBC. |
| format | Article |
| id | doaj-art-dc95bd5943514d139eb975bc6c08f609 |
| institution | DOAJ |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-dc95bd5943514d139eb975bc6c08f6092025-08-20T03:06:51ZengBMCMolecular Medicine1528-36582025-08-0131112410.1186/s10020-025-01336-wTargeting LINC02544/miR-497-5p/CAPRIN1 axis via exosome-based siRNA to overcome immunotherapy resistance in triple-negative breast cancerBin Lian0Jiayi Li1Shihui Tang2Ting Li3Jinping Li4Department of Surgical Oncology, General Hospital of Ningxia Medical UniversityNorthwest University for NationalitiesDepartment of Operating Room, General Hospital of Ningxia Medical Un iversityNingxia Medical UniversityDepartment of Surgical Oncology, General Hospital of Ningxia Medical UniversityAbstract Background Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression, leading to poor clinical outcomes and resistance to targeted therapies. Immunotherapy has shown limited success due to the development of resistance mechanisms. This study aimed to investigate the role of long non-coding RNA LINC02544 in mediating immunotherapy resistance through regulation of the miR-497-5p/CAPRIN1 axis in TNBC. Methods Bioinformatic analyses of TCGA and GEO databases were performed to assess LINC02544 and miR-497-5p expression in TNBC tissues. In vitro experiments evaluated the regulatory effects of LINC02544 on miR-497-5p and CAPRIN1 expression, as well as TNBC cell proliferation and migration. Exosome-mediated siRNA delivery targeting LINC02544 (exo/si-LINC02544) was tested both in vitro and in vivo in combination with a PD-1 inhibitor in a TNBC mouse model. Results LINC02544 was significantly overexpressed in TNBC, while miR-497-5p was downregulated. In vitro, LINC02544 silencing via exo/si-LINC02544 reduced CAPRIN1 levels, upregulated miR-497-5p, and inhibited TNBC cell proliferation and migration. In vivo, exo/si-LINC02544 combined with PD-1 blockade suppressed tumor growth and enhanced immune cell infiltration. Conclusions Targeting the LINC02544/miR-497-5p/CAPRIN1 axis with exosome-based siRNA delivery represents a promising therapeutic strategy to overcome immunotherapy resistance in TNBC.https://doi.org/10.1186/s10020-025-01336-wTriple-negative breast cancerLINC02544MiR-497-5pImmunotherapy resistanceExosome-based SiRNA delivery |
| spellingShingle | Bin Lian Jiayi Li Shihui Tang Ting Li Jinping Li Targeting LINC02544/miR-497-5p/CAPRIN1 axis via exosome-based siRNA to overcome immunotherapy resistance in triple-negative breast cancer Molecular Medicine Triple-negative breast cancer LINC02544 MiR-497-5p Immunotherapy resistance Exosome-based SiRNA delivery |
| title | Targeting LINC02544/miR-497-5p/CAPRIN1 axis via exosome-based siRNA to overcome immunotherapy resistance in triple-negative breast cancer |
| title_full | Targeting LINC02544/miR-497-5p/CAPRIN1 axis via exosome-based siRNA to overcome immunotherapy resistance in triple-negative breast cancer |
| title_fullStr | Targeting LINC02544/miR-497-5p/CAPRIN1 axis via exosome-based siRNA to overcome immunotherapy resistance in triple-negative breast cancer |
| title_full_unstemmed | Targeting LINC02544/miR-497-5p/CAPRIN1 axis via exosome-based siRNA to overcome immunotherapy resistance in triple-negative breast cancer |
| title_short | Targeting LINC02544/miR-497-5p/CAPRIN1 axis via exosome-based siRNA to overcome immunotherapy resistance in triple-negative breast cancer |
| title_sort | targeting linc02544 mir 497 5p caprin1 axis via exosome based sirna to overcome immunotherapy resistance in triple negative breast cancer |
| topic | Triple-negative breast cancer LINC02544 MiR-497-5p Immunotherapy resistance Exosome-based SiRNA delivery |
| url | https://doi.org/10.1186/s10020-025-01336-w |
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