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Protein regulator of cytokinesis 1 accentuates cholangiocarcinoma progression via mTORC1-mediated glycolysis

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Abstract

This study aimed to investigate the expression of protein regulator of cytokinesis 1 (PRC1) in cholangiocarcinoma (CHOL) and elucidate its potential impact as well as the underlying mechanisms governing the progression of CHOL. In this study, we used CHOL cells (HUCCT1, RBE, and CCLP1) and conducted a series of experiments, including qRT-PCR, cell counting kit-8 assays, EdU assays, flow cytometry, wound healing assays, Transwell assays, western blotting, double luciferase assays, and ELISA. Subsequently, a mouse model was established using cancer cell injections. Haematoxylin–eosin staining, along with Ki67 and TUNEL assays, were employed to assess tissue histopathology, cell proliferation, and apoptosis. Our findings revealed significantly elevated PRC1 expression in CHOL. According to bioinformatics analysis, it was found that the increased PRC1 level is correlated with the high tumour grades, metastases, and unfavourable prognoses. Notably, PRC1 knockdown inhibited cell viability, proliferation, migration, and invasion while promoting apoptosis in CHOL cells. Analysing TCGA-CHOL data and utilising transcription factor prediction tools (hTFtarget and HumanTFDB), we identified that genes positively correlated with PRC1 in TCGA-CHOL intersect with predicted transcription factors, revealing the activation of PRC1 by forkhead box protein M1 (FOXM1). Moreover, PRC1 was found to exert regulatory control over glycolysis and the mammalian target of rapamycin complex 1 (mTORC1) pathway in the context of CHOL based on KEGG and GSEA analysis. Collectively, these results underscore the pivotal role of PRC1 in CHOL progression, wherein it modulates glycolysis and the mTORC1 pathway under the regulatory influence of FOXM1.

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Availability of data and material

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

This study was supported by the Linyi Science and Technology Development Plan project (202120067).

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, 324 Jingwuwei 7Th Road, Jinan, 250021, Shandong, People’s Republic of China

    Chao Zhang & Chengkun Qin

  2. Department of Hepatobiliary Surgery, Linyi People’s Hospital, Linyi, 276034, Shandong, People’s Republic of China

    Chao Zhang

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  1. Chao Zhang
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  2. Chengkun Qin
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Contributions

CZ designed the study; CZ performed the research; CQ analysed data, and wrote the paper.

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Correspondence to Chengkun Qin.

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The authors declare that they have no conflicts of interest.

Ethics approval and consent to participate

All methods were carried out in accordance with relevant guidelines and regulations of the Declaration of Helsinki. The studies involving human participants were reviewed and approved by the Ethics Committee of Shandong Provincial Hospital Affiliated to Shandong University (SWYX: NO. 2022-317). The patients/participants provided their written informed consent to participate in this study. The experimental protocol of our study was performed in accordance with the Guide for the Care and Use of Laboratory Animals and approved by Shandong Provincial Hospital Affiliated to Shandong University (No. 2023-078).

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Zhang, C., Qin, C. Protein regulator of cytokinesis 1 accentuates cholangiocarcinoma progression via mTORC1-mediated glycolysis. Human Cell 37, 739–751 (2024). https://doi.org/10.1007/s13577-024-01032-7

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