Abstract
Prostate cancer (PCa) has long been the leading cause of cancer-associated deaths among male worldwide. Our previous studies have shown that Bloom syndrome protein (BLM) plays a vital role in PCa proliferation, yet the underlying molecular mechanism remains largely obscure. Mechanistically, BLM directly interacted with hepatoma-derived growth factor (HDGF). Functionally, BLM and HDGF knockdown resulted in the higher impairment of PC3 proliferation, clonogenicity, migration and invasion than that their counterpart with either BLM or HDGF knockdown exclusively. Of note, HDGF overexpression expedited, whereas its knockdown suppressed, PC3 proliferation, clonogenicity, migration and invasion. Additionally, the potentiation or attenuation was partially antagonized upon BLM depletion or overexpression. In line with the vitro data, the impact of BLM and HDGF on tumor growth was investigated in mouse xenograft models. ChIP-seq, dual-luciferase reporter and western blotting assays were employed to expound the regulatory network in PC3 cells. The results unveiled that HDGF activated KRAS and suppressed RhoA transcription, and that the function of HDGF was mediated, in part, by interaction with BLM. Accordingly, the MAPK/ERK pathway was activated. Moreover, the regulation of HDGF on KRAS and RhoA had a signal crosstalk. To recapitulate, BLM and HDGF may serve as novel prognostic markers and potential therapeutic targets in PCa.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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The authors acknowledge the financial support received from the National Natural Science Foundation of China (Grant Numbers 31860242).
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Y Ruan conceived the project. M Huang prepared all the materials. Y Guo carried out the in vitro and in vitro experiments. All authors participated in the discussion and evaluation of experimental results. Y Guo completed the first draft and drew the schematic figures. H Xu finalized the manuscript.
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All animal experimental procedures were approved by the Laboratory Animal Ethics Committee of Guizhou University (License Number: EAE-GZU-2022-P001).
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Guo, Y., Xu, H., Huang, M. et al. BLM promotes malignancy in PCa by inducing KRAS expression and RhoA suppression via its interaction with HDGF and activation of MAPK/ERK pathway. J. Cell Commun. Signal. 17, 757–772 (2023). https://doi.org/10.1007/s12079-022-00717-8
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DOI: https://doi.org/10.1007/s12079-022-00717-8