Circular RNA hsa_circ_0000515 acts as a miR-326 sponge to promote cervical cancer progression through up-regulation of ELK1
Circular RNA hsa_circ_0000515 acts as a miR-326 sponge to promote cervical cancer progression through up-regulation of ELK1
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DOI：
10.18632/aging.102356
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发表时间：
2019-11-30
期刊：
影响因子：
5.2
通讯作者：
Xu, Hai
中科院分区：
文献类型：
--
作者：
Tang, Qiu;Chen, Zhigang;Xu, Hai
本研究探讨环状核糖核酸(CircRNA)hsa_circ_0000515在宫颈癌中的作用及其可能的作用机制。HSACIRC 0000515和Ets转录因子ELK1在宫颈癌组织和细胞中高表达，而miR326表达下调。HSA_CIRC_0000515低表达与宫颈癌患者预后良好有关。将一系列模拟物、抑制剂、过表达的质粒或siRNAs导入宫颈癌细胞，以改变hSA_CIRC_0000515、miR-326和ELK1的表达。体外实验表明，沉默hsA_CIRC_0000515或上调miR-326可抑制宫颈癌细胞的增殖和侵袭，并诱导细胞凋亡和自噬。双荧光素酶报告基因分析、核糖核酸下拉实验和核糖核酸印迹分析表明，hSA_CIRC_0000515能够作为miR-326的CENA而增加ELK1。此外，ELK1表达增强可促进宫颈癌细胞的增殖和侵袭，但抑制细胞的凋亡和自噬。体内实验进一步证实了hSA_CIRC_0000515沉默对肿瘤生长的抑制作用。我们的研究结果表明，hSA_CIRC_0000515在宫颈癌中具有促癌作用。本研究为靶向hSA_CIRC_0000515治疗宫颈癌提供了依据。
This study investigates the role of circular RNA (circRNA) hsa_circ_0000515 in cervical cancer and the underlying mechanism associated with microRNA-326 (miR-326). hsa_circ_0000515 and ETS transcription factor ELK1 (ELK1) were initially over-expressed and miR-326 was down-regulated in cervical cancer tissues and cells. Low hsa_circ_0000515 expression was found to be associated with favorable prognosis of patients with cervical cancer. A series of mimics, inhibitors, over-expression plasmids or siRNAs were introduced into cervical cancer cells to alter the expression of hsa_circ_0000515, miR-326 and ELK1. In vitro experiments exhibited that silencing of hsa_ circ_0000515 or upregulation of miR-326 resulted in suppressed proliferation and invasion, along with induced apoptosis and autophagy of cervical cancer cells. Dual-luciferase reporter assay, RNA pull-down and RIP assays highlighted that hsa_circ_0000515 was able to act as a ceRNA of miR-326 to increase ELK1. Furthermore, enhancement of ELK1 expression resulted in enhanced proliferation and invasion but repressed apoptosis and autophagy of cervical cancer cells. In vivo experiments further confirmed the suppressed tumor growth by hsa_ circ_0000515 silencing. Our findings demonstrated that hsa_circ_0000515 acts as a tumor promoter in cervical cancer. The study provides evidence for targeting hsa_circ_0000515 for therapeutic purposes in treating cervical cancer.