CircNR3C1 inhibits proliferation of bladder cancer cells by sponging miR-27a-3p and downregulating cyclin D1 expression

Accumulating evidences suggest that circular RNAs play vital roles in human cancers. Previously, we found that circHIPK3 suppressed invasion of bladder cancer cells via sponging miR-558 and downregulating heparanase expression. In this study, we discovered that a circular RNA derived from NR3C1 (circNR3C1) was downregulated in bladder cancer tissues and cell lines according to RNA-Seq data and qRT-PCR analysis. Functionally, we found that overexpression of circNR3C1 could significantly inhibit cell cycle progression and proliferation of bladder cancer cells in vitro, as well as suppress tumor growth in vivo. Mechanistically, we demonstrated that circNR3C1 possessed four targeting sites of miR-27a-3p and could effectively sponge miR-27a-3p to suppress the expression of cyclin D1. Furthermore, we revealed that miR-27a-3p functioned as an oncogene through interacting with 5'UTR of cyclin D1 to enhance its expression, which led to promote cell cycle progression and proliferation in bladder cancer cells. Conclusively, our findings further confirm the hypothesis that circRNAs function as "microRNA sponges", and our data suggest that circNR3C1 and miR-27a-3p would be potential therapeutic targets for bladder cancer treatment.

越来越多的证据表明，环状RNA在人类癌症中起着至关重要的作用。此前，我们发现circHIPK3通过吸附miR - 558并下调乙酰肝素酶的表达来抑制膀胱癌细胞的侵袭。在本研究中，根据RNA - Seq数据和qRT - PCR分析，我们发现一种源自NR3C1的环状RNA（circNR3C1）在膀胱癌组织和细胞系中表达下调。在功能上，我们发现circNR3C1的过表达在体外可显著抑制膀胱癌细胞的细胞周期进程和增殖，并在体内抑制肿瘤生长。从机制上讲，我们证明circNR3C1具有4个miR - 27a - 3p的靶向位点，能够有效吸附miR - 27a - 3p以抑制细胞周期蛋白D1的表达。此外，我们揭示miR - 27a - 3p通过与细胞周期蛋白D1的5'UTR相互作用增强其表达而作为癌基因发挥作用，从而促进膀胱癌细胞的细胞周期进程和增殖。总之，我们的研究结果进一步证实了环状RNA作为“微小RNA海绵”的假说，并且我们的数据表明circNR3C1和miR - 27a - 3p可能是膀胱癌治疗的潜在治疗靶点。