RNF8 up-regulates AR/ARV7 action to contribute to advanced prostate cancer progression

Tingting Zhou1,2, Shengli Wang1, Xiaoyu Song2

  • 1Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, School of Life Sciences, China Medical University, Shenyang, Liaoning Province, 110122, P. R. China.

Cell Death & Disease
|April 16, 2022
PubMed

Insights

RNF8 promotes prostate cancer (PC) progression and endocrine resistance by upregulating androgen receptor (AR) signaling. Targeting RNF8 may offer a new strategy against treatment-resistant prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Androgen receptor (AR) signaling drives prostate cancer (PC) progression.
  • Androgen deprivation therapy (ADT) resistance is a major challenge in PC treatment.
  • The mechanisms underlying AR and AR variant expression in endocrine resistance are not fully understood.

Purpose of the Study:

  • To investigate the role of RNF8 in prostate cancer progression and endocrine resistance.
  • To elucidate the mechanism by which RNF8 influences AR signaling.
  • To evaluate RNF8 as a potential therapeutic target for castration-resistant PC (CRPC).

Main Methods:

  • Bioinformatics and immunohistochemical analyses of PC and CRPC samples.
  • Correlation analysis of RNF8 expression with clinical parameters (Gleason score, prognosis).
  • Investigation of RNF8's effect on AR transcription, ARV7, c-Myc, and PSA expression in CRPC cells, including assessment of E3 ligase activity and response to enzalutamide treatment.

Main Results:

  • RNF8 is highly expressed in PC and CRPC, correlating positively with Gleason score and predicting poor prognosis.
  • RNF8 upregulates AR transcription via c-Myc and acts as a co-activator for AR/ARV7 at the PSA promoter, modulating histone modifications.
  • RNF8 knockdown reduces AR transactivation and PSA expression, restrains cell proliferation, and alleviates enzalutamide resistance in CRPC cells.

Conclusions:

  • RNF8 plays a critical role in promoting PC progression and endocrine resistance.
  • RNF8 enhances AR signaling through transcriptional and co-activator mechanisms.
  • RNF8 represents a potential therapeutic target for overcoming endocrine resistance in prostate cancer.

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