Sha Jianjun, Xia Lei, Han Qing, Chi Chenfei, Zhu Yinjie, Pan Jiahua, Huang Yiran, Xia Weiliang, Dong Baijun, Xue Wei, Yang Chen
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University Shanghai 200127, China.
School of Biomedical Engineering, Shanghai Jiaotong University Shanghai 200240, China.
Am J Cancer Res. 2020 Dec 1;10(12):4372-4385. eCollection 2020.
Abnormal circular RNA (circRNA) expression correlates with human traits such as many kinds of cancers. Though circRNAs have links to cancer, they have less characterization in metastatic castration-resistant prostate cancer (PCa), which is main reason for PCa mortality. Therefore, high-throughput sequencing was used for selected circRNA profiles. The result showed that circ-TRPS1 was upregulated significantly in high-grade PCa tissues or cell lines. High circ-TRPS1 expression correlated to aggressive PCa phenotypes. Knockdown of circ-TRPS1 suppressed PCa proliferation and metastasis through targeting miR-124-3p/EZH2 axis-mediated stemness in PCa, which was validated by luciferase reporter assays. EZH2 overexpression or miR-124-3p inhibition reversed the inhibition of circ-TRPS1 silencing in PCa cell migration and proliferation by recovering stemness. In summary, data demonstrated that circ-TRPS1 suppressed PCa progression through functioning similar to a miR-124-3p sponge to enhance EZH2 expression and cancer stem-like cell differentiation. Thus, circ-TRPS1 might be a candidate target for PCa treatment.
异常环状RNA（circRNA）表达与多种癌症等人类特征相关。尽管circRNA与癌症有关，但它们在转移性去势抵抗性前列腺癌（PCa）中的特征描述较少，而PCa是前列腺癌死亡的主要原因。因此，采用高通量测序来筛选circRNA谱。结果显示，circ-TRPS1在高级别PCa组织或细胞系中显著上调。circ-TRPS1高表达与侵袭性PCa表型相关。敲低circ-TRPS1可通过靶向miR-124-3p/EZH2轴介导的PCa干性来抑制PCa增殖和转移，荧光素酶报告基因检测验证了这一点。EZH2过表达或miR-124-3p抑制通过恢复干性逆转了circ-TRPS1沉默对PCa细胞迁移和增殖的抑制作用。总之，数据表明circ-TRPS1通过类似于miR-124-3p海绵的功能来增强EZH2表达和癌症干细胞样细胞分化，从而抑制PCa进展。因此，circ-TRPS1可能是PCa治疗的候选靶点。
