Department of Urology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha City 410008, Hunan Province, PR China.
Department of Oncology, Xiangya Hospital of Central South University, No.87 Xiangya Road, Changsha City 410008, Hunan Province, PR China.
Int J Biol Macromol. 2024 Jan;256(Pt 1):128338. doi: 10.1016/j.ijbiomac.2023.128338. Epub 2023 Nov 24.
Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent urological carcinomas with a low overall 5-year survival rate, and its prognosis remains dismal. circular RNAs (circRNAs) has been discovered to be important regulators in ccRCC. However, the specific regulatory mechanisms of circRNAs and their impact on phenotypes require further in-depth research. circRNA microarray sequencing analysis was used in this study to explore the expression pattern of circRNAs in ccRCC. circWSB1 was discovered, and we evaluated its derivation, potential diagnostic efficacy, and prognostic significance in ccRCC tissues. We discovered that circWSB1 is highly expressed in ccRCC. We identified that circWSB1 interacts with miR-182-5p and upregulates the expression of its host gene, WSB1. Through models in vivo and in vitro models, we found that circWSB1 increases WSB1 expression via the circWSB1/miR-182-5p/WSB1 axis, which promotes ccRCC cell proliferation and migration. The high expression of circWSB1 and WSB1 is correlated with poorer clinical prognosis and pathological grading. circWSB1 diminishes the inhibitory impact of miR-182-5p on WSB1 and increases WSB1 expression, thereafter promoting ccRCC development. Our findings provide a promising predictive biomarker and therapeutic target for ccRCC.
透明细胞肾细胞癌(ccRCC)是最常见的泌尿系统癌之一,总体 5 年生存率较低,预后仍然不佳。环状 RNA(circRNAs)已被发现是 ccRCC 中的重要调控因子。然而,circRNAs 的具体调控机制及其对表型的影响需要进一步深入研究。本研究采用 circRNA 微阵列测序分析来探讨 circRNAs 在 ccRCC 中的表达模式。发现 circWSB1,并评估其在 ccRCC 组织中的衍生、潜在诊断效力和预后意义。我们发现 circWSB1 在 ccRCC 中高表达。我们确定 circWSB1 与 miR-182-5p 相互作用,并上调其宿主基因 WSB1 的表达。通过体内和体外模型,我们发现 circWSB1 通过 circWSB1/miR-182-5p/WSB1 轴增加 WSB1 表达,促进 ccRCC 细胞增殖和迁移。circWSB1 和 WSB1 的高表达与较差的临床预后和病理分级相关。circWSB1 减弱了 miR-182-5p 对 WSB1 的抑制作用,增加了 WSB1 的表达,进而促进了 ccRCC 的发展。我们的研究结果为 ccRCC 提供了有前途的预测生物标志物和治疗靶点。