环状 RNA hsa_circ_0068871 通过靶向 miR-181a-5p 调控 FGFR3 表达并激活 STAT3 促进膀胱癌进展。
Circular RNA hsa_circ_0068871 regulates FGFR3 expression and activates STAT3 by targeting miR-181a-5p to promote bladder cancer progression.
机构信息
Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China.
Department of Urology, Qilu Hospital of Shandong University, Jinan, 250012, China.
出版信息
J Exp Clin Cancer Res. 2019 Apr 18;38(1):169. doi: 10.1186/s13046-019-1136-9.
BACKGROUND
FGFR3 plays an important role in the development of bladder cancer (BCa). Hsa_circ_0068871 is a circRNA generated from several exons of FGFR3. However, the potential functional role of hsa_circ_0068871 in BCa remains largely unknown. Here we aim to evaluate the role of hsa_circ_0068871 in BCa.
METHODS
We selected miR-181a-5p as the potential target miRNA of hsa_circ_0068871. The expression levels of hsa_circ_0068871 and miR-181a-5p were examined in BCa tissues and paired adjacent normal tissues by quantitative real-time PCR. To characterize the function of hsa_circ_0068871, BCa cell lines were stably infected with lentivirus targeting hsa_circ_0068871, followed by examinations of cell proliferation, migration and apoptosis. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0068871 in BCa. Biotinylated RNA probe pull-down assay, fluorescence in situ hybridization and luciferase reporter assay were conducted to confirm the relationship between hsa_circ_0068871, miR-181a-5p and FGFR3.
RESULTS
Hsa_circ_0068871 is over-expressed in BCa tissues and cell lines, whereas miR-181a-5p expression is repressed. Depletion of has_circ_0068871 or upregulation of miR-181a-5p inhibited the proliferation and migration of BCa cells in vitro and in vivo. Mechanistically, hsa_circ_0068871 upregulated FGFR3 expression and activated STAT3 by targeting miR-181a-5p to promote BCa progression.
CONCLUSIONS
Hsa_circ_0068871 regulates the miR-181a-5p/FGFR3 axis and activates STAT3 to promote BCa progression, and it may serve as a potential biomarker.
背景
FGFR3 在膀胱癌（BCa）的发展中起着重要作用。Hsa_circ_0068871 是一种由 FGFR3 的几个外显子产生的 circRNA。然而，hsa_circ_0068871 在 BCa 中的潜在功能作用在很大程度上仍然未知。在这里，我们旨在评估 hsa_circ_0068871 在 BCa 中的作用。
方法
我们选择 miR-181a-5p 作为 hsa_circ_0068871 的潜在靶 miRNA。通过定量实时 PCR 检测 BCa 组织和配对的相邻正常组织中 hsa_circ_0068871 和 miR-181a-5p 的表达水平。为了表征 hsa_circ_0068871 的功能，BCa 细胞系被靶向 hsa_circ_0068871 的慢病毒稳定感染，然后检查细胞增殖、迁移和凋亡。此外，在裸鼠中进行异种移植实验以评估 hsa_circ_0068871 在 BCa 中的作用。Biotinylated RNA 探针下拉测定、荧光原位杂交和荧光素酶报告基因测定用于证实 hsa_circ_0068871、miR-181a-5p 和 FGFR3 之间的关系。
结果
hsa_circ_0068871 在 BCa 组织和细胞系中过表达，而 miR-181a-5p 的表达受到抑制。hsa_circ_0068871 的耗竭或 miR-181a-5p 的上调抑制了 BCa 细胞在体外和体内的增殖和迁移。机制上，hsa_circ_0068871 通过靶向 miR-181a-5p 上调 FGFR3 表达并激活 STAT3，促进 BCa 进展。
结论
hsa_circ_0068871 调节 miR-181a-5p/FGFR3 轴并激活 STAT3 促进 BCa 进展，它可能作为一种潜在的生物标志物。
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