Department of Urology Surgery, The Chongqing General Hospital, Chongqing, China.
Neoplasma. 2020 May;67(3):584-594. doi: 10.4149/neo_2020_190621N534. Epub 2020 Mar 18.
Prostate cancer (Pca) is the second frequent malignancy in men. Long noncoding RNAs (lncRNAs) have been reported to play essential roles in the progression of cancers, including Pca. LncRNA colorectal neoplasia differentially expressed (CRNDE) has been found to affect tumorigenesis in many cancers. However, the exact role and mechanism of CRNDE in Pca remain poorly understood. 64 Pca patients were recruited in this study. PC3 and 22RV1 cells were used in vitro experiments. The expressions of CRNDE, microRNA-101 (miR-101), and Ras-related protein 1A (Rap1A) were detected in vivo and in vitro by quantitative real-time polymerase chain reaction and western blot, respectively. Cell proliferation, apoptosis, migration, and invasion were investigated through cell counting kit-8, flow cytometry, and Transwell assays, respectively. The interaction between miR-101 and CRNDE or Rap1A was explored by bioinformatics analysis and luciferase reporter assay. High expression of CRNDE was shown in Pca tissues and cells and predicted poor outcomes of patients. Overexpression of CRNDE promoted cell proliferation, migration, and invasion but decreased apoptosis in Pca cells, while its knockdown showed an opposite effect. CRNDE was a decoy of miR-101 and its effect on Pca progression was reversed by miR-101. Rap1A was identified as a target of miR-101 and it attenuated the effect of miR-101 on Pca development. Moreover, the Rap1A protein level was positively regulated by CRNDE, which was weakened by miR-101. CRNDE contributed to cell proliferation, migration, and invasion by regulating the miR-101/Rap1A axis in Pca, providing a novel strategy for Pca treatment.
前列腺癌（Pca）是男性第二大常见恶性肿瘤。长链非编码 RNA（lncRNA）已被报道在癌症的进展中发挥重要作用，包括 Pca。lncRNA 结直肠肿瘤差异表达（CRNDE）已被发现影响许多癌症的肿瘤发生。然而，CRNDE 在 Pca 中的确切作用和机制仍知之甚少。本研究招募了 64 名 Pca 患者。在体外实验中使用了 PC3 和 22RV1 细胞。通过定量实时聚合酶链反应和 Western blot 分别检测了体内和体外的 CRNDE、microRNA-101（miR-101）和 Ras 相关蛋白 1A（Rap1A）的表达。通过细胞计数试剂盒-8、流式细胞术和 Transwell 分析分别研究了细胞增殖、凋亡、迁移和侵袭。通过生物信息学分析和荧光素酶报告基因分析探讨了 miR-101 与 CRNDE 或 Rap1A 的相互作用。结果显示，CRNDE 在 Pca 组织和细胞中高表达，预测患者预后不良。CRNDE 过表达促进 Pca 细胞增殖、迁移和侵袭，而减少凋亡，而其敲低则显示相反的效果。CRNDE 是 miR-101 的诱饵，其对 Pca 进展的影响可被 miR-101 逆转。Rap1A 被鉴定为 miR-101 的靶标，它减弱了 miR-101 对 Pca 发育的影响。此外，CRNDE 蛋白水平受 miR-101 正向调节，而 miR-101 则减弱了 Rap1A 的作用。CRNDE 通过调节 miR-101/Rap1A 轴促进 Pca 细胞的增殖、迁移和侵袭，为 Pca 治疗提供了新的策略。
