Circular RNA circFOXO3 promotes prostate cancer progression through sponging miR-29a-3p
Circular RNA circFOXO3 promotes prostate cancer progression through sponging miR-29a-3p
复制标题
环状RNA circFOXO3通过海绵miR-29a-3p促进前列腺癌进展
DOI：
10.1111/jcmm.14791
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发表时间：
2019-11-16
影响因子：
5.3
通讯作者：
Li, Yao
中科院分区：
文献类型：
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作者：
Kong, Zhe;Wan, Xuechao;Li, Yao
FOXO 3（CircularRNAFOXO 3，也称Hsa_circ_0006404）来源于FOXO 3基因的外显子2，在不同疾病中有异常表达。然而，circFOXO 3是否在前列腺癌（PCa）的肿瘤发生和进展中发挥重要作用仍不清楚。在这项研究中，我们发现circFOXO 3在PCa组织和血清样品中均上调。此外，circFOXO 3与PCa样本中的Gleason评分呈正相关。与格里森评分= 6的PCa样品相比，观察到CircFOXO 3在格里森评分> 6的PCa样品中上调。在体外，敲低circFOXO 3可显著抑制PCa细胞的周期和增殖，促进细胞凋亡。此外，我们通过生物信息学分析、双荧光素酶报告基因分析和生物素化RNA pull-down分析证明circFOXO 3可以作为miR-29 a-3 p海绵上调SLC 25 A15的表达。SLC 25 A15可以逆转PCa中敲低circFOXO 3的肿瘤抑制作用。值得注意的是，我们发现miR-29 a-3 p下调;然而，与正常组织相比，SLC 25 A15在PCa样品中过表达。总之，circFOXO 3作为miR-29 a-3 p海绵发挥作用，表现出致癌活性，通过转录上调SLC 25 A15影响PCa中的细胞周期和细胞凋亡。我们的分析表明，circFOXO 3可以作为有前途的前列腺癌生物标志物。
Circular RNA FOXO3 (CircFOXO3, also termed as Hsa_circ_0006404) is derived from exon 2 of forkhead box O3 (FOXO3) gene, and abnormal expression is shown in different diseases. However, whether circFOXO3 plays important roles in tumorigenesis and progression of prostate cancer (PCa) remains unclear. In this study, we found that circFOXO3 was up-regulated in both PCa tissues and serum samples. Moreover, circFOXO3 was positively correlated with the Gleason score in PCa samples. CircFOXO3 was observed to be up-regulated in Gleason score > 6 PCa samples compared with Gleason score = 6 PCa samples. Knock-down circFOXO3 could remarkably inhibit PCa cell cycle, proliferation and promote cell apoptosis in vitro. Furthermore, we demonstrated circFOXO3 could act as miR-29a-3p sponge to up-regulate SLC25A15 expression by bioinformatics analysis, dual-luciferase reporter assays and biotinylated RNA pull-down assays. SLC25A15 could reverse the tumour suppressing roles of knock-down circFOXO3 in PCa. Of note, we found that miR-29a-3p was down-regulated; however, SLC25A15 was overexpressed in PCa samples compared with normal tissues. In conclusion, circFOXO3 acts as a miR-29a-3p sponge to exhibit oncogenic activity that affects the cell cycle and cell apoptosis in PCa through transcriptional up-regulation of SLC25A15. Our analysis suggests circFOXO3 could act as promising prostate cancer biomarkers.