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.
基金:
National Natural Science Foundation of China (National Science Foundation of China) [2022YFC3602904]; National key RD plan of China [82303052]; National Natural Science Foundation of China [2023B1111030006]; Key R&D Plan of Guangdong Province [2021A0505030085]; International Science and technology cooperation project plan of Guangdong Province [2019005]; Sun Yat-Sen University Clinical Research 5010 Program [mnzl202001]; Beijing Bethune Charitable Foundation [202206010117]; Guangzhou Science and Technology Key RD Project [Y-MSDZD2022-0760, Y-tongshu2021/ms-0162]; Beijing Xisike Clinical Oncology Research Foundation [2023A1515011905]; Applied Basic Research Foundation [2023M741577]; China Postdoctoral Science Foundation
第一作者单位:[1]Southern Med Univ, Nanfang Hosp, Dept Urol, Guangzhou 510515, Peoples R China[2]Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA
共同第一作者:
通讯作者:
通讯机构:[3]Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Urol, Guangzhou 510120, Peoples R China[5]Guangzhou Med Univ, Qingyuan Peoples Hosp, Affiliated Hosp 6, Dept Urol, Qingyuan 511518, Peoples R China
推荐引用方式(GB/T 7714):
Wang Qiong,Cheng Bisheng,Singh Sandeep,et al.A protein-encoding CCDC7 circular RNA inhibits the progression of prostate cancer by up-regulating FLRT3[J].NPJ PRECISION ONCOLOGY.2024,8(1):doi:10.1038/s41698-024-00503-2.
APA:
Wang, Qiong,Cheng, Bisheng,Singh, Sandeep,Tao, Yiran,Xie, Zhongqiu...&Huang, Hai.(2024).A protein-encoding CCDC7 circular RNA inhibits the progression of prostate cancer by up-regulating FLRT3.NPJ PRECISION ONCOLOGY,8,(1)
MLA:
Wang, Qiong,et al."A protein-encoding CCDC7 circular RNA inhibits the progression of prostate cancer by up-regulating FLRT3".NPJ PRECISION ONCOLOGY 8..1(2024)