YAP1 inhibits circRNA-000425 expression and thus promotes oncogenic activities of miR-17 and miR-106
YAP1 inhibits circRNA-000425 expression and thus promotes oncogenic activities of miR-17 and miR-106
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YAP1 抑制 circRNA-000425 表达，从而促进 miR-17 和 miR-106 的致癌活性
DOI：
10.1016/j.bbrc.2018.06.163
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发表时间：
2018-09-18
影响因子：
3.1
通讯作者：
Deng, Jun
中科院分区：
文献类型：
--
作者：
Liu, Zhen;Huang, Shanshan;Deng, Jun
YAP 1是Hippo信号通路的重要效应子，通过转录调控一系列参与细胞增殖、凋亡和药物敏感性等信号通路的靶基因，促进肿瘤的发生发展。近年来，人们发现环状RNA（circular RNA，circRNA）在转录后调控基因的表达，成为基因调控的一个新层次。然而，circRNA是否在YAP 1诱导的肿瘤发生中发挥作用仍然很难理解。在这里，我们将circRNA-000425确定为YAP 1的新抑制靶点，并且还发现它与miR-17/miR-106 b结合，从而抑制由这些miRNA诱导的癌细胞生长。通过对从用或不用YAP 1 siRNA处理的细胞中提取的RNA进行circRNA微阵列分析，揭示了circRNA-000425是YAP 1靶标，并通过RT-q-PCR和ChIP测定进一步证实。有趣的是，生物信息学分析、荧光素酶测定和RT-q-PCR结果显示，circRNA-000425与miR-17和miR-106 b结合，但不与let-7a结合，并且挽救了miR-17/miR-106对p21和BIM表达的抑制作用。此外，集落形成和MTT测定显示circRNA-000425抑制由miR-17诱导的癌细胞生长。这些发现揭示了YAP 1通过转录抑制circRNA-000425表达促进miR-17和miR-106 b致癌活性的机制。(C)2018爱思唯尔公司All rights reserved.
YAP1, a vital effector of Hippo pathway, promotes cancer development via transcriptionally regulating a batch of target genes involved in various signaling pathways, including proliferation, apoptosis, and cell drug sensitivity. Recently, circular RNAs (circRNAs) have been shown to control gene expression post transcriptionally and become a new layer of gene regulation. However, whether circRNAs play roles in YAP1-induced tumorigenesis is still largely elusive. Here, we identify circRNA-000425 as a new inhibitory target of YAP1, and also find that it binds to miR-17/miR-106b, and thus suppresses cancer cell growth induced by these miRNAs. circRNA-000425 is revealed as a YAP1 target through circRNA microarray analysis of RNAs extracted from cells treated with or without YAP1 siRNAs, and further confirmed by RT-q-PCR and ChIP assays. Interestingly, bioinformatics analysis, luciferase assay, and RT-q-PCR results showed that circRNA-000425 binds to miR-17 and miR-106b, but not let-7a, and rescues the inhibitory effect of miR-17/miR-106 on the expressions of both p21 and BIM. In addition, colony formation and MTT assay showed that circRNA-000425 inhibits cancer cell growth induced by miR-17. These findings reveal a mechanism by which YAP1 promotes oncogenic activities of miR-17 and miR-106b through transcriptionally inhibiting circRNA-000425 expression. (C) 2018 Elsevier Inc. All rights reserved.