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ARPC1A is regulated by STAT3 to inhibit ferroptosis and promote prostate cancer progression

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Abstract

The aim of this study was to investigate the biological function and molecular mechanism of ARPC1A (actin related protein 2/3 complex subunit 1A) in prostate cancer progression. RT–qPCR and IHC results showed that the level of ARPC1A in prostate cancer tissues was significantly higher than that in adjacent tissues. The results of TCGA (the cancer genome atlas) database analysis showed that high expression of ARPC1A indicates poor prognosis in prostate cancer patients. In vitro functional experiments confirmed that downregulation of ARPC1A expression resulted in decreased cell viability and invasive ability of prostate cancer cells, as ARPC1A knockdown promoted ferroptosis. The transcriptional regulation mechanism of STAT3 (signal transduction and activators of transcription 3) on ARPC1A was elucidated by Co-IP, ChIP and luciferase reporter assays. In vivo experiments also supported the in vitro results. We propose that reduced ARPC1A expression inhibits prostate cancer cell viability and invasion in a ferroptotic manner. The ARPC1A level may serve as an independent predictor of prognosis in prostate cancer patients.

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Availability of data and materials

The data and materials that were used or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

PCa:

Prostate cancer

ARPC1A:

Actin-related protein 2/3 complex subunit 1A

STAT3:

Signal transducer and activator of transcription 3

GPX4:

Glutathione peroxidase 4

SLC7A11:

Solute carrier family 7 member 11

PTGS2:

Prostaglandin endoperoxide synthase 2

GEPIA:

Gene expression profiling interactive analysis

MTT:

3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide

Co-IP:

Coimmunoprecipitation

ChIP:

Chromatin immunoprecipitation

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Acknowledgements

We thank Professor Yuanjie Niu for his guidance and assistance in certain experiments.

Funding

This work was supported by the Nankai University Young Teachers Research Start-up Project (5e9eac077be828a2017c81d74e873ed9, to Dr. Shen).

Author information

Authors and Affiliations

  1. Department of Urology Surgery, The Third Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan, People’s Republic of China

    Junpeng Ji & Wenjun Wang

  2. Department of Urology Surgery, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan, People’s Republic of China

    Huibing Li

  3. School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China

    Bo Yuan & Tianyu Shen

Authors
  1. Junpeng Ji
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  2. Huibing Li
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  5. Tianyu Shen
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Contributions

TS and JJ designed the experiments. JJ and BY performed the cell biology experiments molecular biology experiments. HL performed the animal experiments and participated in the sequence alignment. WW and BY performed the statistical analysis. TS and JJ analyzed the data and wrote the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Tianyu Shen.

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Conflict of interest

The authors declare that they have no competing interests.

Ethics approval and consent to participate

The clinical experimental protocols were approved by the Ethics Committee of The Third Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology Medical. The clinical trial ethics approval number is No. 20220301. Written informed consent was obtained from all patients. The study was conducted in accordance with the Declaration of Helsinki. The animal experimental protocols were approved by the Ethics Committee of The Third Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology Medical. The animal experiment ethics approval number is No. 20220302.

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Ji, J., Li, H., Wang, W. et al. ARPC1A is regulated by STAT3 to inhibit ferroptosis and promote prostate cancer progression. Human Cell 35, 1591–1601 (2022). https://doi.org/10.1007/s13577-022-00754-w

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