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Related Experiment Video

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Phthalate exposure induces microRNA-5010/Nrf2-EGR1/GDF15 signaling expression in prostate cancer.

Yuh-Shyan Tsai1, Yeong-Chin Jou2, Ian Seng Cheong3

  • 1Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Ecotoxicology and Environmental Safety
|January 21, 2025
PubMed
Summary

Phthalate exposure, specifically DEHP metabolites, is linked to increased prostate cancer aggressiveness. This occurs through microRNA regulation, activating Nrf-2 signaling and downstream genes like GDF15, impacting tumor progression.

Keywords:
GDF-15Nrf-2microRNAphthalate esterprostate cancer

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Area of Science:

  • Environmental Health
  • Oncology
  • Molecular Biology

Background:

  • Phthalate exposure is associated with prostate enlargement via hormonal changes and oxidative stress.
  • The precise role and mechanisms of phthalates in prostate cancer development and progression are not fully understood.

Purpose of the Study:

  • To investigate the association between phthalate exposure and prostate cancer.
  • To elucidate the underlying molecular mechanisms, including microRNA and signaling pathway involvement.

Main Methods:

  • Analysis of urinary phthalate metabolites (DEHP) in prostate biopsy and prostatectomy patient cohorts using HPLC-MS and ELISA.
  • Small RNA sequencing to identify microRNA expression changes in relation to phthalate exposure and cancer stage.
  • In vitro studies in prostate cancer cells to assess the impact of DEHP on Nrf-2 signaling and GDF15 expression.

Main Results:

  • Significantly higher urinary MEOHP and ΣDEHP metabolite levels were found in prostate cancer patients compared to benign cases.
  • MIR-5010 was upregulated and MIR-205 downregulated in prostate cancer, with MIR-5010 linked to Nrf-2 pathway activation.
  • DEHP exposure in vitro increased Nrf-2 signaling, EGR-1, and GDF15 expression, and urinary GDF15 correlated with phthalate metabolites and markers of aggressiveness.

Conclusions:

  • Phthalate exposure, particularly DEHP, may contribute to prostate cancer aggressiveness.
  • The mechanism involves microRNA-mediated regulation of the Nrf-2/EGR-1/GDF15 signaling pathway.
  • Urinary GDF15 levels could serve as a potential biomarker for phthalate-induced prostate cancer progression.