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Comprehensive Characterization of Androgen-Responsive circRNAs in Prostate Cancer

Zhe Kong1, Yali Lu1, Xuechao Wan1

  • 1Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, China.

Life (Basel, Switzerland)
|October 23, 2021
PubMed

Insights

Androgen-responsive circular RNAs (circRNAs) are implicated in prostate cancer progression. This study identified key circRNAs and RNA-binding proteins, revealing potential diagnostic biomarkers like circNFIA and circZNF561.

Area of Science:

  • Molecular Biology
  • Genomics
  • Oncology

Background:

  • The androgen receptor (AR) signaling pathway is crucial in prostate cancer development.
  • Circular RNAs (circRNAs) are novel noncoding RNAs with emerging roles in disease.
  • The function of androgen-responsive circRNAs in prostate cancer is largely unknown.

Purpose of the Study:

  • To identify and characterize androgen-responsive circRNAs in prostate cancer.
  • To investigate the regulatory mechanisms of these circRNAs by the androgen receptor.
  • To explore the potential roles of specific circRNAs (circNFIA, circZNF561) as diagnostic biomarkers.

Main Methods:

  • Microarray analysis to identify androgen-responsive circRNAs and mRNAs after dihydrotestosterone (DHT) stimulation.
  • Bioinformatic analysis using the circInteractome database to identify RNA-binding proteins.
  • Expression analysis of circNFIA and circZNF561 in prostate cancer tissues and patient plasma.

Main Results:

  • Identified 3237 androgen-responsive circRNAs and 1954 androgen-responsive mRNAs.
  • Discovered AR regulates circRNA expression transcriptionally and post-transcriptionally via alternative splicing.
  • Identified WTAP and TNRC6 as key RNA-binding proteins involved in androgen-responsive circRNA biogenesis.
  • circNFIA is upregulated and acts as an oncogene, while circZNF561 is downregulated and acts as a tumor suppressor in prostate cancer.
  • circNFIA and circZNF561 show potential as diagnostic biomarkers in prostate cancer tissues and plasma.

Conclusions:

  • Androgen-responsive circRNAs play significant roles in prostate cancer progression.
  • circNFIA and circZNF561 are potential diagnostic biomarkers for prostate cancer.
  • Understanding circRNA regulation by AR provides insights into prostate cancer mechanisms.
Keywords:
TNRC6WTAPandrogen-responsive circRNAcircNFIA and circZNF561prostate cancer

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