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Down regulation of U2AF1 promotes ARV7 splicing and prostate cancer progression

Hongwen Cao1, Dan Wang1, Renjie Gao1

  • 1Surgical Department I (Urology Department), Longhua Hospital Shanghai University of Traditional Chinese Medicine, No. 725 Wanping Road South, Xuhui District, Shanghai, 200032, China.

Biochemical and Biophysical Research Communications
|January 21, 2021
PubMed

Insights

U2 Small Nuclear RNA Auxiliary Factor 1 (U2AF1) downregulation promotes prostate cancer cell proliferation and resistance to anti-androgen therapy by affecting androgen receptor variant 7 (ARV7) splicing, impacting patient prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer often develops resistance to anti-androgen treatments.
  • Androgen receptor variant 7 (ARV7) is implicated in treatment resistance.
  • The role of U2 Small Nuclear RNA Auxiliary Factor 1 (U2AF1) in this process is not fully understood.

Purpose of the Study:

  • To investigate the role of U2AF1 in anti-androgen resistance in prostate cancer.
  • To elucidate the underlying molecular mechanisms, including its relationship with ARV7 and Mitogen-Activated Protein Kinase 1 (MAPK1).

Main Methods:

  • U2AF1 and ARV7 knockdown and overexpression in PC3 and DU145 cells.
  • Construction of a bicalutamide-resistant PC3 (PC3 BR) cell line.
  • Assays for cell proliferation (cell count, MTT, soft agar).
  • qRT-PCR for mRNA levels of U2AF1, ARV7, and MAPK1.
  • Western blot for MAPK1 protein expression.

Main Results:

  • U2AF1 downregulation correlated with poor prognosis in prostate cancer patients.
  • A negative correlation was observed between ARV7 and U2AF1 in tumor tissues.
  • U2AF1 downregulation promoted prostate cancer cell proliferation and bicalutamide resistance.
  • U2AF1 regulated ARV7 splicing, which was associated with MAPK1.

Conclusions:

  • U2AF1 plays a critical role in prostate cancer cell proliferation and resistance to anti-androgen therapy.
  • U2AF1 influences anti-androgen resistance by regulating ARV7 splicing, involving MAPK1.
  • U2AF1 downregulation is a potential biomarker for poor prognosis in prostate cancer.
Keywords:
ARV7Bicalutamide-resistanceMAPK1Prostate cancerU2AF1

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