State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University Cancer Center, Guangzhou, China.
Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Clin Cancer Res. 2018 Dec 15;24(24):6319-6330. doi: 10.1158/1078-0432.CCR-18-1270. Epub 2018 Oct 10.
Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial-mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells' EMT and explored their regulatory mechanisms and clinical significance in UCBs.
We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells' EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes, and , in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA).
We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis.
CircPRMT5 exerts critical roles in promoting UCB cells' EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.
环状 RNA（circRNAs）作为一类新的非编码 RNA，最近在人类癌症的发病机制中引起了广泛关注。然而，circRNAs 在癌症细胞上皮-间充质转化（EMT）中的作用尚不清楚。在本研究中，我们旨在鉴定新型环状 RNA，以调控膀胱癌（UCB）细胞 EMT，并探索其在 UCB 中的调控机制和临床意义。
我们首先使用环状 RNA 微阵列筛选配对的 UCB 和正常组织中的环状 RNA 表达谱，然后在大量 UCB 患者中研究上调的环状 RNA circPRMT5 的临床意义。我们进一步研究了 circPRMT5 在 UCB 细胞 EMT 中的功能和潜在机制。此外，我们评估了 circPRMT5 对 miR-30c 及其靶基因 和 的调控作用，在我们研究所和癌症基因组图谱（TCGA）的两个独立队列中进行了验证。
我们证明了上调的 circPRMT5 表达与 UCB 患者的晚期临床分期和较差的生存相关。我们进一步揭示了 circPRMT5 通过海绵 miR-30c 促进 UCB 细胞 EMT。来自两个独立 UCB 队列的临床分析表明，circPRMT5/miR-30c/SNAIL1/E-cadherin 通路在支持 UCB 进展中至关重要。重要的是，我们发现 circPRMT5 在 UCB 患者的血清和尿液外泌体中上调，并且与肿瘤转移显著相关。
circPRMT5 在促进 UCB 细胞 EMT 和/或侵袭性方面发挥着关键作用，是该疾病的预后生物标志物，表明 circPRMT5 可能成为 UCB 患者的一种可利用的治疗靶点。
