Liu Bo, Qian Duocheng, Zhou Weidong, Jiang Huiyang, Xiang Zhendong, Wu Denglong
Department of Urology, Tongji Hospital, Tongji University of Medicine, Shanghai, China.
Department of Urology, Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China.
Front Oncol. 2021 Feb 4;10:620306. doi: 10.3389/fonc.2020.620306. eCollection 2020.
Prostate cancer (PCa) is one of the most common types of tumors among males worldwide. However, the roles of long noncoding RNAs (lncRNAs) in PCa remain unclear. This study shows that lncRNA FAM83H-AS1 is upregulated in prostate adenocarcinoma, bladder urothelial carcinoma, and kidney renal papillary cell carcinoma samples. Androgen receptor (AR) signaling plays the most important role in PCa tumorigenesis and development. In this study, the results validate that AR signaling is involved in upregulating FAM83H-AS1 expression in PCa cells. Loss-of-function assays demonstrate that FAM83H-AS1 acts as an oncogene in PCa by modulating cell proliferation, cell cycle, and migration. Bioinformatics analysis demonstrates that FAM83H-AS1 is remarkably related to the regulation of the cell cycle and DNA replication through affecting multiple regulators related to these pathways, such as CCNE2. Mechanically, we found that FAM83H-AS1 plays its roles through sponging miR-15a to promote CCNE2 expression. These findings indicate that FAM83H-AS1 is a novel diagnostic and therapeutic marker for PCa.
前列腺癌(PCa)是全球男性中最常见的肿瘤类型之一。然而,长链非编码RNA(lncRNAs)在PCa中的作用仍不清楚。本研究表明,lncRNA FAM83H-AS1在前列腺腺癌、膀胱尿路上皮癌和肾肾乳头状细胞癌样本中上调。雄激素受体(AR)信号通路在PCa的发生和发展中起最重要的作用。在本研究中,结果证实AR信号通路参与上调PCa细胞中FAM83H-AS1的表达。功能丧失实验表明,FAM83H-AS1通过调节细胞增殖、细胞周期和迁移在PCa中作为癌基因发挥作用。生物信息学分析表明,FAM83H-AS1通过影响与这些途径相关的多个调节因子(如CCNE2),与细胞周期和DNA复制的调节显著相关。从机制上讲,我们发现FAM83H-AS1通过海绵化miR-15a来促进CCNE2表达发挥其作用。这些发现表明,FAM83H-AS1是PCa的一种新型诊断和治疗标志物。