RNA binding protein ILF3 increases CEP55 mRNA stability to enhance malignant potential of breast cancer cells and suppress ferroptosis
Abstract Background Ferroptosis has emerged as a promising therapeutic target in cancer treatment. CEP55, a key regulator of cell mitosis, plays a significant role in the tumorigenesis of many malignancies. In this study, we elucidated the function of CEP55 in the ferroptosis of breast cancer (BC)....
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BMC
2025-01-01
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| Series: | Hereditas |
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| Online Access: | https://doi.org/10.1186/s41065-025-00372-0 |
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| author | Sheng Chen Yangyong Luo Simin Ruan Guosen Su Guoxing Huang |
| author_facet | Sheng Chen Yangyong Luo Simin Ruan Guosen Su Guoxing Huang |
| author_sort | Sheng Chen |
| collection | DOAJ |
| description | Abstract Background Ferroptosis has emerged as a promising therapeutic target in cancer treatment. CEP55, a key regulator of cell mitosis, plays a significant role in the tumorigenesis of many malignancies. In this study, we elucidated the function of CEP55 in the ferroptosis of breast cancer (BC). Methods The protein levels of CEP55 and ILF3 were detected by immunoblotting or immunohistochemistry, and their mRNA levels were assessed by quantitative PCR. Cell invasion and migration were evaluated by transwell assay. Cell apoptosis and colony formation were tested by flow cytometry and colony formation assays, respectively. RNA immunoprecipitation (RIP) experiment and CEP55 mRNA stability assay were used to validate the relationship between ILF3 and CEP55 mRNA. Subcutaneous xenograft studies were performed to analyze the role of ILF3 depletion in tumor growth. Results CEP55 and ILF3 were upregulated in most of human BC samples and MDA-MB-231 and MCF-7 BC cells. The depletion of CEP55 or ILF3 impaired the growth, invasion, and migration of MDA-MB-231 and MCF-7 cells, while promoted their ferroptosis and apoptosis. Mechanistically, ILF3 stabilized CEP55 mRNA to regulate CEP55 expression in BC cells. CEP55 restoration partially rescued the malignant potential defects of ILF3-depleted BC cells and attenuates their ferroptosis. Moreover, ILF3 depletion enhanced the anti-tumor growth activity of the ferroptosis inducer erastin in MDA-MB-231 subcutaneous xenograft tumors. Conclusion Our observations indicate that the depletion of ILF3 impairs the malignant potential of BC cells and promotes their ferroptosis by downregulating CEP55 expression. Silencing ILF3 or CEP55 could represent a potential therapeutic strategy for BC treatment. Graphical abstract |
| format | Article |
| id | doaj-art-3aa814597f7b42d0abe80dd95d665699 |
| institution | Kabale University |
| issn | 1601-5223 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Hereditas |
| spelling | doaj-art-3aa814597f7b42d0abe80dd95d6656992025-02-02T12:27:40ZengBMCHereditas1601-52232025-01-01162111310.1186/s41065-025-00372-0RNA binding protein ILF3 increases CEP55 mRNA stability to enhance malignant potential of breast cancer cells and suppress ferroptosisSheng Chen0Yangyong Luo1Simin Ruan2Guosen Su3Guoxing Huang4Department of Breast Disease, GaoZhou People’HospitalDepartment of Breast Disease, GaoZhou People’HospitalDepartment of Breast Disease, GaoZhou People’HospitalDepartment of Breast Disease, GaoZhou People’HospitalDepartment of Breast Disease, GaoZhou People’HospitalAbstract Background Ferroptosis has emerged as a promising therapeutic target in cancer treatment. CEP55, a key regulator of cell mitosis, plays a significant role in the tumorigenesis of many malignancies. In this study, we elucidated the function of CEP55 in the ferroptosis of breast cancer (BC). Methods The protein levels of CEP55 and ILF3 were detected by immunoblotting or immunohistochemistry, and their mRNA levels were assessed by quantitative PCR. Cell invasion and migration were evaluated by transwell assay. Cell apoptosis and colony formation were tested by flow cytometry and colony formation assays, respectively. RNA immunoprecipitation (RIP) experiment and CEP55 mRNA stability assay were used to validate the relationship between ILF3 and CEP55 mRNA. Subcutaneous xenograft studies were performed to analyze the role of ILF3 depletion in tumor growth. Results CEP55 and ILF3 were upregulated in most of human BC samples and MDA-MB-231 and MCF-7 BC cells. The depletion of CEP55 or ILF3 impaired the growth, invasion, and migration of MDA-MB-231 and MCF-7 cells, while promoted their ferroptosis and apoptosis. Mechanistically, ILF3 stabilized CEP55 mRNA to regulate CEP55 expression in BC cells. CEP55 restoration partially rescued the malignant potential defects of ILF3-depleted BC cells and attenuates their ferroptosis. Moreover, ILF3 depletion enhanced the anti-tumor growth activity of the ferroptosis inducer erastin in MDA-MB-231 subcutaneous xenograft tumors. Conclusion Our observations indicate that the depletion of ILF3 impairs the malignant potential of BC cells and promotes their ferroptosis by downregulating CEP55 expression. Silencing ILF3 or CEP55 could represent a potential therapeutic strategy for BC treatment. Graphical abstracthttps://doi.org/10.1186/s41065-025-00372-0Breast cancerFerroptosisCEP55RNA binding proteinILF3 |
| spellingShingle | Sheng Chen Yangyong Luo Simin Ruan Guosen Su Guoxing Huang RNA binding protein ILF3 increases CEP55 mRNA stability to enhance malignant potential of breast cancer cells and suppress ferroptosis Hereditas Breast cancer Ferroptosis CEP55 RNA binding protein ILF3 |
| title | RNA binding protein ILF3 increases CEP55 mRNA stability to enhance malignant potential of breast cancer cells and suppress ferroptosis |
| title_full | RNA binding protein ILF3 increases CEP55 mRNA stability to enhance malignant potential of breast cancer cells and suppress ferroptosis |
| title_fullStr | RNA binding protein ILF3 increases CEP55 mRNA stability to enhance malignant potential of breast cancer cells and suppress ferroptosis |
| title_full_unstemmed | RNA binding protein ILF3 increases CEP55 mRNA stability to enhance malignant potential of breast cancer cells and suppress ferroptosis |
| title_short | RNA binding protein ILF3 increases CEP55 mRNA stability to enhance malignant potential of breast cancer cells and suppress ferroptosis |
| title_sort | rna binding protein ilf3 increases cep55 mrna stability to enhance malignant potential of breast cancer cells and suppress ferroptosis |
| topic | Breast cancer Ferroptosis CEP55 RNA binding protein ILF3 |
| url | https://doi.org/10.1186/s41065-025-00372-0 |
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