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ARPC5 is transcriptionally activated by KLF4, and promotes cell migration and invasion in prostate cancer via up-regulating ADAM17

ARPC5 serves as an oncogene in prostate cancer

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Abstract

Background: Prostate cancer (PCa) is one of the most common cancers in men worldwide. Actin-related protein 2/3 complex subunit 5 (ARPC5) has been validated as a critical regulator in several kinds of human tumors. However, whether ARPC5 is implicated in PCa progression remains largely unknown. Methods: PCa specimens and PCa cell lines were obtained for detecting gene expressions using western blot and quantitative reverse transcriptase PCR (qRT-PCR). PCa cells transfected with ARPC5 shRNA or a disintegrin and metalloprotease 17 (ADAM17) overexpressed plasmids were harvested for assessing cell proliferation, migration and invasion by using cell counting kit-8 (CCK-8), colony formation and transwell assays, respectively. The interaction relationship between molecules was testified with chromatin immunoprecipitation and luciferase reporter assay. Xenograft mice model was conducted for confirming the role of ARPC5/ADAM17 axis in vivo. Results: Upregulated ARPC5 was observed in PCa tissues and cells, as well as forecasted poor prognosis of PCa patients. Depletion of ARPC5 inhibited PCa cell proliferation, migration and invasion. Krüppel-like factor 4 (KLF4) was identified to be a transcriptional activator of ARPC5 via binding with its promoter region. Furthermore, ADAM17 served as a downstream effector of ARPC5. ADAM17 overexpression overturned ARPC5 knockdown-induced repressive impacts on PCa progression in vitro and in vivo. Conclusion: Collectively, ARPC5 was activated by KLF4 and upregulated ADAM17 to promote PCa progression, which might act as a promising therapeutic target and prognostic biomarker for PCa.

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Data Availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

Arp2/3 complex:

actin-related protein 2/3 complex

ARPC5:

actin-related protein 2/3 complex subunit 5

KLF4:

krüppel-like factor 4

ADAM:

a disintegrin and metalloprotease

PCa:

prostate cancer

qRT-PCR:

quantitative reverse transcriptase PCR

CCK-8:

cell counting kit-8

KMT2D:

histone lysine methyltransferase 2D

MMP-2:

matrix metalloproteinase-2

MMP-9:

matrix metalloproteinase-9

LASP1:

LIM and SH3 protein 1

YAP:

Yes-associated protein 1

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Acknowledgements

We would like to give our sincere gratitude to the reviewers for their constructive comments.

Funding

This work was supported by Zhuzhou Science and Technology Plan Project (2021-007).

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Authors and Affiliations

  1. Department of Urology, ZhuZhou central hospital, No. 116, Changjiang South Road, Tianyuan District, ZhuZhou, 412000, Hunan Province, P.R. China

    GenYi Qu, YuLong Zhang, Cheng Tang, Guang Yang, Dan Chen & Yong Xu

  2. Department of Ultrasound, ZhuZhou central hospital, ZhuZhou, 412000, Hunan Province, P.R. China

    HongTao Duan

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  1. GenYi Qu
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Contributions

GenYi Qu: Conceptualization, Methodology, Supervision, Writing- Original draft preparation, Investigation, Writing- Reviewing and Editing

YuLong Zhang: Software

HongTao Duan: Visualization

Cheng Tang: Validation

Guang Yang: Data curation

Dan Chen: Data curation

Yong Xu: Conceptualization, Supervision, Writing- Original draft preparation, Writing- Reviewing and Editing.

Corresponding author

Correspondence to Yong Xu.

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Ethics approval and consent to participate

In this study, a total of 42 pairs of PCa tissues and its matched normal adjacent tissues were gathered from PCa patients who received surgical resection at ZhuZhou central hospital from 2019 to 2022, with informed consent from all patients. The patients enrolled had not received preoperative chemotherapy or radiotherapy. The tissues were preserved in liquid nitrogen for subsequent experiments. This present research was approved by the Ethics Committee of ZhuZhou central hospital. The experimental protocols were approved by the Ethical Commission of the Animal Care in ZhuZhou central hospital.

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The informed consent was obtained from all participants.

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The authors declare no competing interests.

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Supplementary Material 1

The mRNA expressions of ADAMs (ADAM9, ADAM10, ADAM12, ADAM15, ADAM17) were detected after silencing ARPC5 in PC3 and DU145 cells. All experiments were repeated three times. And data are presented as the mean ? standard deviation. *p < 0.05, **p < 0.01, ***p < 0.001.

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Qu, G., Zhang, Y., Duan, H. et al. ARPC5 is transcriptionally activated by KLF4, and promotes cell migration and invasion in prostate cancer via up-regulating ADAM17. Apoptosis 28, 783–795 (2023). https://doi.org/10.1007/s10495-023-01827-3

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