J Cancer 2024; 15(13):4097-4112. doi:10.7150/jca.96306 This issue Cite
Research Paper
1. Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University, Qujing City 655000, Yunnan Province, People's Republic of China.
2. Department of the Medical Oncology / the Hebei Key Laboratory of the Cancer Radiotherapy and Chemotherapy; the Affiliated Hospital of Hebei University; Baoding City 071000, Hebei province, People's Republic of China.
3. Institute of Infectious Diseases, Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, 100 Middle Street of 4th West Ring Road, Beijing, 100039, China.
*Mingsheng Liu and Chenxiang Xu equally contribute to this work.
Ferroptosis has been characterized as non-apoptotic programmed cell death and is considered a novel strategy for antitumor treatment. The factor that binds to inducer of short transcripts‐1 (FBI-1) is an important proto‐oncogene playing multiple roles in human malignancies and the development of resistance to therapy. However, the roles of FBI-1 in ferroptosis of endocrine independent prostate carcinoma are still unknown. The results of this study showed that FBI-1 inhibited the ferroptosis of prostate carcinoma PC-3 cells (a typical endocrine-independent prostate carcinoma cell line) via the miR-324-3p/glutathione peroxidase 4 (miR-324-3p/GPX4) axis. Overexpression of FBI-1 enhanced the expression levels of GPX4. In contrast, knockdown of FBI-1 decreased the expression of GPX4 and induced the ferroptosis of PC-3 cells. The miR-324-3p decreased the expression of GPX4 by targeting the 3'-untranslated region of GPX4 to induce ferroptosis. Notably, FBI-1 increased the expression of GPX4 by repressing the levels of miR-324-3p. The transcription of miR-324-3p was mediated by specificity protein 1 (SP1), and FBI-1 repressed the expression of miR-324-3p by repressing the activation of SP1. In clinical specimens, the endogenous levels of FBI-1 were positively associated with Glutathione Peroxidase 4 (GPX4) and negatively related with the expression of miR-324-3p. Therefore, the results indicated that the miR-324-3p/GPX4 axis participates in the FBI-1-mediated ferroptosis of prostate carcinoma cells.
Keywords: factor that binds to the inducer of short transcripts-1, glutathione peroxidase 4, miRNA-324-3p