1. Academic Validation
  2. A protein-encoding CCDC7 circular RNA inhibits the progression of prostate cancer by up-regulating FLRT3

A protein-encoding CCDC7 circular RNA inhibits the progression of prostate cancer by up-regulating FLRT3

  • NPJ Precis Oncol. 2024 Jan 16;8(1):11. doi: 10.1038/s41698-024-00503-2.
Qiong Wang # 1 2 Bisheng Cheng # 3 Sandeep Singh 2 Yiran Tao 3 Zhongqiu Xie 2 Fujun Qin 2 Xinrui Shi 2 Jingjing Xu 3 4 Chenxi Hu 1 Wanlong Tan 1 Hui Li 5 Hai Huang 6 7
Affiliations

Affiliations

  • 1 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
  • 2 Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
  • 3 Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
  • 4 Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 5 Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA. hl9r@virginia.edu.
  • 6 Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. huangh9@mail.sysu.edu.cn.
  • 7 Department of Urology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, China. huangh9@mail.sysu.edu.cn.
  • # Contributed equally.
Abstract

Circular RNAs (circRNAs) are a family of endogenous RNAs that have become a focus of biological research in recent years. Emerging evidence has revealed that circRNAs exert biological functions by acting as transcriptional regulators, MicroRNA sponges, and binding partners with RNA-binding proteins. However, few studies have identified coding circRNAs, which may lead to a hidden repertoire of proteins. In this study, we unexpectedly discovered a protein-encoding circular RNA circCCDC7(15,16,17,18,19) while we were searching for prostate Cancer related chimeric RNAs. circCCDC7(15,16,17,18,19) is derived from exon 19 back spliced to exon 15 of the CCDC7 gene. It is significantly downregulated in patients with high Gleason score. Prostate Cancer patients with decreased circCCDC7(15,16,17,18,19) expression have a worse prognosis, while linear CCDC7 had no such association. Overexpressed circCCDC7(15,16,17,18,19) inhibited prostate Cancer cell migration, invasion, and viability, supporting classification of circCCDC7(15,16,17,18,19) as a bona fide tumor suppressor gene. We provide evidence that its tumor suppressive activity is driven by the protein it encodes, and that circCCDC7(15,16,17,18,19) encodes a secretory protein. Consistently, conditioned media from circCCDC7(15,16,17,18,19) overexpressing cells has the same tumor suppressive activity. We further demonstrate that the tumor suppressive activity of circCCDC7(15,16,17,18,19) is at least partially mediated by FLRT3, whose expression also negatively correlates with Gleason score and clinical prognosis. In conclusion, circCCDC7(15,16,17,18,19) functions as a tumor suppressor in prostate Cancer cells through the circCCDC7-180aa secretory protein it encodes, and is a promising therapeutic peptide for prostate Cancer.

Figures
Products