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Article

MicroRNA‑15a promotes prostate cancer cell ferroptosis by inhibiting GPX4 expression

  • Authors:
    • Po Xu
    • Ying Wang
    • Zhe Deng
    • Zhibo Tan
    • Xiaojuan Pei
  • View Affiliations / Copyright

    Affiliations: Department of Emergency, The First Affiliated Hospital, Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong 518000, P.R. China, Medical Oncology Ward 1, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Shenzhen, Guangdong 518116, P.R. China, Department of Radiation Oncology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518100, P.R. China, Department of Pathology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong 518100, P.R. China
  • Article Number: 67
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    Published online on: January 3, 2022
       https://doi.org/10.3892/ol.2022.13186
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Abstract

Ferroptosis is a novel form of regulated cell death characterized by accumulated lipid reactive oxygen species (ROS) and inactivation of glutathione peroxidase 4 (GPX4). The present study aimed to investigate the role of microRNA (miRNA/miR)‑15a in ferroptosis of prostate cancer cells. Bioinformatics analysis was performed to predict the potential interaction between miR‑15a and the 3'‑untranslated region (UTR) of GPX4 mRNA. The prostate cancer cell line, LNCAP was transfected with miR‑15a mimics or small interfering (si)‑GPX4. Reverse transcription‑quantitative PCR and western blot analyses were performed to detect the mRNA and protein expression levels of GPX4, respectively. Biotin‑RNA pull‑down and dual‑luciferase reporter assays were performed to verify the interaction between miR‑15a and GPX4 mRNA. The Cell Counting Kit‑8 assay was performed to assess cell proliferation, while lactate dehydrogenase (LDH) and intracellular ferrous iron levels were detected via ELISA. Lipid ROS and mitochondrial membrane potential (MMP) were assessed via flow cytometry and staining with C11‑BIODIPY probes or JC‑1. Furthermore, lipid peroxidation was identified by measuring malondialdehyde (MDA) levels. The results demonstrated that transfection with miR‑15a mimics decreased GPX4 protein expression. Bioinformatics analysis revealed potential binding sites between miR‑15a and the 3'‑UTR region of GPX4, and RNA pull‑down and the dual‑luciferase reporter assays further confirmed the interaction between miR‑15a and GPX4 mRNA. Both transfection with miR‑15a mimics and si‑GPX4 suppressed cell proliferation, elevated LDH release, accumulated intracellular ferrous iron and ROS, disrupted MMP and increased MDA levels. Taken together, the results of the present study suggest miR‑15a induces ferroptosis by regulating GPX4 in prostate cancer cells, which provides evidence for investigating the therapeutic strategies of prostate cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Xu P, Wang Y, Deng Z, Tan Z and Pei X: MicroRNA‑15a promotes prostate cancer cell ferroptosis by inhibiting GPX4 expression. Oncol Lett 23: 67, 2022.
APA
Xu, P., Wang, Y., Deng, Z., Tan, Z., & Pei, X. (2022). MicroRNA‑15a promotes prostate cancer cell ferroptosis by inhibiting GPX4 expression. Oncology Letters, 23, 67. https://doi.org/10.3892/ol.2022.13186
MLA
Xu, P., Wang, Y., Deng, Z., Tan, Z., Pei, X."MicroRNA‑15a promotes prostate cancer cell ferroptosis by inhibiting GPX4 expression". Oncology Letters 23.2 (2022): 67.
Chicago
Xu, P., Wang, Y., Deng, Z., Tan, Z., Pei, X."MicroRNA‑15a promotes prostate cancer cell ferroptosis by inhibiting GPX4 expression". Oncology Letters 23, no. 2 (2022): 67. https://doi.org/10.3892/ol.2022.13186
Copy and paste a formatted citation
x
Spandidos Publications style
Xu P, Wang Y, Deng Z, Tan Z and Pei X: MicroRNA‑15a promotes prostate cancer cell ferroptosis by inhibiting GPX4 expression. Oncol Lett 23: 67, 2022.
APA
Xu, P., Wang, Y., Deng, Z., Tan, Z., & Pei, X. (2022). MicroRNA‑15a promotes prostate cancer cell ferroptosis by inhibiting GPX4 expression. Oncology Letters, 23, 67. https://doi.org/10.3892/ol.2022.13186
MLA
Xu, P., Wang, Y., Deng, Z., Tan, Z., Pei, X."MicroRNA‑15a promotes prostate cancer cell ferroptosis by inhibiting GPX4 expression". Oncology Letters 23.2 (2022): 67.
Chicago
Xu, P., Wang, Y., Deng, Z., Tan, Z., Pei, X."MicroRNA‑15a promotes prostate cancer cell ferroptosis by inhibiting GPX4 expression". Oncology Letters 23, no. 2 (2022): 67. https://doi.org/10.3892/ol.2022.13186
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