Mechanism of LINC00958 in ferroptosis of breast cancer through the SRSF1/GPX4 axis
Abstract Background Breast cancer (BC) is the most common cancer among women. Ferroptosis is a novel iron-dependent form of cell death and affects cancer development. This study was conducted to explore the role of long intergenic non-protein coding RNA958 (LINC00958) in the ferroptosis of BC cells....
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| Language: | English |
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BMC
2025-06-01
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| Series: | Hereditas |
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| Online Access: | https://doi.org/10.1186/s41065-025-00469-6 |
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| author | Shan Wang Xinlu Liu Xiaoli Hou Wei Sun Jiajie Chen Yasen Cao Hong Cheng |
| author_facet | Shan Wang Xinlu Liu Xiaoli Hou Wei Sun Jiajie Chen Yasen Cao Hong Cheng |
| author_sort | Shan Wang |
| collection | DOAJ |
| description | Abstract Background Breast cancer (BC) is the most common cancer among women. Ferroptosis is a novel iron-dependent form of cell death and affects cancer development. This study was conducted to explore the role of long intergenic non-protein coding RNA958 (LINC00958) in the ferroptosis of BC cells. Methods The expression levels of LINC00958 and glutathione peroxidase 4 (GPX4) in BC cell lines were first determined. After the interference of LINC00958, cell proliferation was assessed by cell counting kit-8 and colony formation assays, and ferroptosis was tested by measurements of ferric ion content, reactive oxygen species (ROS), glutathione (GSH), and acyl-CoA synthetase long-chain family member 4 (ACSL4). The binding of serine/arginine splicing factor 1 (SRSF1) to LINC00958/GPX4 was analyzed by RNA immunoprecipitation. GPX4 mRNA stability was determined after actinomycin D treatment. Rescue experiments were conducted to test the role of GPX4 in ferroptosis. Finally, mouse transplantation tumors were designed to verify the role of LINC00958. Results LINC00958 was highly-expressed in BC cells. LINC00958 downregulation inhibited proliferation and promoted ferroptosis, while LINC00958 overexpression promoted proliferation and inhibited ferroptosis. LINC00958 directly bound to SRSF1, increased the occupancy of SRSF1 on GPX4 mRNA, and augmented the mRNA stability of GPX4. GPX4 overexpression neutralized the promotive role of LINC00958 downregulation in ferroptosis of BC cells. Conclusion Binding of LINC00958 to SRSF1 increases the occupancy of SRSF1 on GPX4 mRNA and the mRNA stability and expression of GPX4, thereby inhibiting ferroptosis of BC cells. |
| format | Article |
| id | doaj-art-77830eb4909d433c9e74ac216ce4e8d5 |
| institution | Kabale University |
| issn | 1601-5223 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | Hereditas |
| spelling | doaj-art-77830eb4909d433c9e74ac216ce4e8d52025-08-20T03:47:14ZengBMCHereditas1601-52232025-06-01162111110.1186/s41065-025-00469-6Mechanism of LINC00958 in ferroptosis of breast cancer through the SRSF1/GPX4 axisShan Wang0Xinlu Liu1Xiaoli Hou2Wei Sun3Jiajie Chen4Yasen Cao5Hong Cheng6Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University Medical College, Yangzhou UniversityThe Second People’s Hospital of Lianyungang City (Cancer Hospital of Lianyungang)Department of Medical Science, Yangzhou Polytechnic CollegeJiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University Medical College, Yangzhou UniversityJiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University Medical College, Yangzhou UniversityJiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University Medical College, Yangzhou UniversityJiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University Medical College, Yangzhou UniversityAbstract Background Breast cancer (BC) is the most common cancer among women. Ferroptosis is a novel iron-dependent form of cell death and affects cancer development. This study was conducted to explore the role of long intergenic non-protein coding RNA958 (LINC00958) in the ferroptosis of BC cells. Methods The expression levels of LINC00958 and glutathione peroxidase 4 (GPX4) in BC cell lines were first determined. After the interference of LINC00958, cell proliferation was assessed by cell counting kit-8 and colony formation assays, and ferroptosis was tested by measurements of ferric ion content, reactive oxygen species (ROS), glutathione (GSH), and acyl-CoA synthetase long-chain family member 4 (ACSL4). The binding of serine/arginine splicing factor 1 (SRSF1) to LINC00958/GPX4 was analyzed by RNA immunoprecipitation. GPX4 mRNA stability was determined after actinomycin D treatment. Rescue experiments were conducted to test the role of GPX4 in ferroptosis. Finally, mouse transplantation tumors were designed to verify the role of LINC00958. Results LINC00958 was highly-expressed in BC cells. LINC00958 downregulation inhibited proliferation and promoted ferroptosis, while LINC00958 overexpression promoted proliferation and inhibited ferroptosis. LINC00958 directly bound to SRSF1, increased the occupancy of SRSF1 on GPX4 mRNA, and augmented the mRNA stability of GPX4. GPX4 overexpression neutralized the promotive role of LINC00958 downregulation in ferroptosis of BC cells. Conclusion Binding of LINC00958 to SRSF1 increases the occupancy of SRSF1 on GPX4 mRNA and the mRNA stability and expression of GPX4, thereby inhibiting ferroptosis of BC cells.https://doi.org/10.1186/s41065-025-00469-6LINC00958Breast cancerSRSF1GPX4FerroptosisRNA-binding protein |
| spellingShingle | Shan Wang Xinlu Liu Xiaoli Hou Wei Sun Jiajie Chen Yasen Cao Hong Cheng Mechanism of LINC00958 in ferroptosis of breast cancer through the SRSF1/GPX4 axis Hereditas LINC00958 Breast cancer SRSF1 GPX4 Ferroptosis RNA-binding protein |
| title | Mechanism of LINC00958 in ferroptosis of breast cancer through the SRSF1/GPX4 axis |
| title_full | Mechanism of LINC00958 in ferroptosis of breast cancer through the SRSF1/GPX4 axis |
| title_fullStr | Mechanism of LINC00958 in ferroptosis of breast cancer through the SRSF1/GPX4 axis |
| title_full_unstemmed | Mechanism of LINC00958 in ferroptosis of breast cancer through the SRSF1/GPX4 axis |
| title_short | Mechanism of LINC00958 in ferroptosis of breast cancer through the SRSF1/GPX4 axis |
| title_sort | mechanism of linc00958 in ferroptosis of breast cancer through the srsf1 gpx4 axis |
| topic | LINC00958 Breast cancer SRSF1 GPX4 Ferroptosis RNA-binding protein |
| url | https://doi.org/10.1186/s41065-025-00469-6 |
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