研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

鉴定 circATG9A 作为肾细胞癌的新型生物标志物。

Identification of circATG9A as a novel biomarker for renal cell carcinoma.

发表日期:2023 Nov 09
作者: Ye Shen, Ruipeng Wu, Zou Zhuo, Ximeng Deng, Weijian Li, Changkun Liu
来源: CANCER GENE THERAPY

摘要:

肾细胞癌(RCC)的发病率和死亡率在全球范围内迅速增加。为了获得关于环状 RNA (circRNA) 在 RCC 进展中的调节作用的新见解,我们对三对 ccRCC 和邻近正常组织进行了 RNA 测序。 RT-PCR用于分析RNA表达。我们通过各种检测(包括 CCK-8、Transwell、伤口愈合和集落形成检测)研究了 circATG9A 对 RCC 细胞的影响。此外,我们采用 FISH、RNA Pull-down、荧光素酶报告基因和 RIP 检测来阐明 circATG9A 调节 RCC 的机制。最终,我们鉴定出了 118 个在 RCC 中差异表达的 circRNA,其中包括一种新的 circRNA circATG9A,它被发现在体外和体内均可促进 RCC 进展。此外,mRNA测序、蛋白质印迹和拯救实验表明TRPM3是RCC进展中circATG9A的靶标。生物信息分析、RNA pull-down、FISH 和 RIP 测定表明 circATG9A 通过充当 miR-497-5p 的海绵来调节 TRPM3 表达。最后,蛋白质印迹显示circATG9A通过Wnt/β-catenin信号通路促进上皮间质转化(EMT)过程。我们的研究结果表明,circATG9A 是一种在 RCC 中上调的新型 circRNA,通过 miR-497-5p/TRPM3/Wnt/β-catenin 轴在 EMT 过程中发挥着至关重要的作用。这些结果表明,circATG9A 可能成为 RCC 预后和治疗的一个有前景的靶标。© 2023。作者,获得 Springer Nature America, Inc. 的独家许可。
The incidence and mortality rates of renal cell carcinoma (RCC) have rapidly increased worldwide. To gain new insights into the regulatory role of circular RNAs (circRNAs) in RCC progression, we conducted RNA sequencing on three pairs of ccRCC and adjacent normal tissues. RT-PCR was utilized to analyze RNA expression. We investigated the effects of circATG9A on RCC cells through various assays including CCK-8, Transwell, wound healing, and colony formation assays. Furthermore, we employed FISH, RNA pull-down, luciferase reporter, and RIP assays to elucidate the mechanism by which circATG9A regulates RCC. Ultimately, we identified 118 differentially expressed circRNAs in RCC, including a novel circRNA, circATG9A, which was found to promote RCC progression both in vitro and in vivo. Moreover, mRNA sequencing, western blotting, and rescue experiments indicated that TRPM3 is the target of circATG9A in RCC progression. Bioinformatic analysis, RNA pull-down, FISH, and RIP assays suggested that circATG9A regulates TRPM3 expression by acting as a sponge for miR-497-5p. Finally, Western blotting revealed that circATG9A promotes the epithelial-mesenchymal transition (EMT) process through the Wnt/β-catenin signaling pathway. Our findings demonstrate that circATG9A is a novel circRNA upregulated in RCC that plays a crucial role in the EMT process through the miR-497-5p/TRPM3/Wnt/β-catenin axis. These results suggest that circATG9A could be a promising target for RCC prognosis and therapy.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.