4.6 Article

Comprehensive Characterization of Androgen-Responsive circRNAs in Prostate Cancer

Journal

LIFE-BASEL
Volume 11, Issue 10, Pages -

Publisher

MDPI
DOI: 10.3390/life11101096

Keywords

prostate cancer; androgen-responsive circRNA; WTAP; TNRC6; circNFIA and circZNF561

Funding

  1. Shanghai Science and Technology Development Foundation [20ZR1404500]
  2. Chinas 13th Five Year Programs for the prevention and cure of great infectious diseases [2018ZX10731301-001-005]
  3. Open Research Funds of the State Key Laboratory of Genetic Engineering, Fudan University [SKLGE-1901]

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The androgen receptor (AR) signaling pathway is crucial in prostate cancer development. We identified numerous androgen-responsive circRNAs and mRNAs, suggesting a potential regulatory role of AR in circRNA expression. Furthermore, the dysregulated circRNAs circNFIA and circZNF561 may serve as diagnostic biomarkers for prostate cancer.
The androgen receptor (AR) signaling pathway plays an important role in the initiation and progression of prostate cancer. Circular RNAs (circRNAs), the novel noncoding RNAs without 5 ' to 3 ' polarity or 3 ' poly (A), play an important role in multiple diseases. However, the potential roles of androgen-responsive circRNAs in prostate cancer remain unclear. In this study, we identified 3237 androgen-responsive circRNAs and 1954 androgen-responsive mRNAs after dihydrotestosterone (DHT) stimulation using microarray. Among them, the expression of 1296 androgen-responsive circRNAs was consistent with that of their parent genes, and we thought AR might regulate the expression of these circRNAs at the transcriptional level. In addition, 1941 circRNAs expression was not consistent with their parent genes, and we speculated that AR may regulate the expression of those circRNAs at the posttranscriptional level through affecting alternative splicing. Analyzing the androgen-responsive circRNAs regulated at the posttranscriptional level, we identified two key RNA binding proteins (RBPs), WTAP and TNRC6, using the circInteractome database, which may play important role in the biogenesis of androgen-responsive circRNAs. Furthermore, we explored the potential biological functions and predicted the molecular mechanisms of two dysregulated circRNAs (circNFIA and circZNF561) in prostate cancer. In this study, we revealed that circNFIA was upregulated in prostate cancer tissues and plasma samples from patients with prostate cancer; circNFIA may play an oncogenic role in prostate cancer. In contrast, circZNF561 was downregulated and may act as a tumor suppressor in prostate cancer. Our results suggest that androgen-responsive circRNAs might regulate the progression of prostate cancer and could be novel diagnostic biomarkers.

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