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The spliceosome as a new therapeutic vulnerability in aggressive prostate cancer

Cheng Zou1, Dingxiao Zhang1

  • 1College of Biology, Hunan University, Changsha, China.

Molecular & Cellular Oncology
|September 18, 2020
PubMed

Insights

Alternative splicing, specifically intron retention, indicates stemness and aggressiveness in prostate cancer. Targeting spliceosome abnormalities offers a new therapeutic strategy for aggressive disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer progression involves complex molecular changes.
  • Alternative splicing (AS) plays a critical role in cancer development.
  • The role of AS in prostate cancer evolution is not fully understood.

Purpose of the Study:

  • To investigate alternative splicing patterns throughout prostate cancer evolution.
  • To identify AS events linked to stemness and tumor aggressiveness.
  • To explore the therapeutic potential of targeting AS in aggressive prostate cancer.

Main Methods:

  • Comprehensive analysis of alternative splicing across the prostate cancer spectrum.
  • Investigation of intron retention as a key AS event.
  • Examination of androgen receptor's role in splicing regulation.

Main Results:

  • Intron retention is identified as a hallmark of stemness and aggressive prostate cancer.
  • Androgen receptor regulates a distinct splicing program separate from its transcriptional control.
  • Aberrant spliceosome activity creates a vulnerable landscape in aggressive tumors.

Conclusions:

  • Alternative splicing, particularly intron retention, is a critical driver of prostate cancer stemness and aggressiveness.
  • Targeting spliceosome dysfunction presents a novel therapeutic vulnerability for aggressive prostate cancer.
  • Understanding AS provides new insights into prostate cancer biology and treatment strategies.
Keywords:
Alternative splicingCRPCE7107cancer treatmentprostate cancerspliceosome

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