Circular RNA BCRC-3 suppresses bladder cancer proliferation through miR-182-5p/p27 axis.
Circular RNA BCRC-3 suppresses bladder cancer proliferation through miR-182-5p/p27 axis.
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环状 RNA BCRC-3 通过 miR-182-5p/p27 轴抑制膀胱癌增殖。
DOI：
10.1186/s12943-018-0892-z
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发表时间：
2018-10-03
期刊：
影响因子：
37.3
通讯作者：
Jiang G
中科院分区：
文献类型：
--
作者：
Xie F;Li Y;Wang M;Huang C;Tao D;Zheng F;Zhang H;Zeng F;Xiao X;Jiang G
环状RNA（circular RNA，circRNA）是近年来发现的一类新的非编码RNA（noncoding RNA，ncRNA），是基因表达的重要调控因子。我们的前期研究已经发现circHIPK 3与膀胱癌的分级、浸润以及淋巴结转移呈负相关。然而，circRNA在膀胱癌细胞增殖中的作用在很大程度上仍然未知。我们对人体组织中的circRNA进行了高通量测序分析，确定膀胱癌相关circRNA-3（BCRC-3，GenBank：KU921434.1）为来源于PSMD 1基因的新的候选circRNA。采用实时定量PCR（qRT-PCR）检测circRNA、mRNA和miRNA在人体组织和细胞中的表达水平。通过体外和体内质粒转染探讨BCRC-3对癌细胞的影响。采用RNA pull down实验、荧光素酶报告基因实验和荧光原位杂交技术验证BCRC-3与microRNA的相互作用。采用流式细胞术、western blot和qRT-PCR检测茉莉酸甲酯（MJ）的抗肿瘤作用。BCRC-3在膀胱癌组织和细胞系中呈低表达。BCRC-3的异位表达在体外和体内均能抑制BC细胞的增殖。从机制上讲，BCRC-3的过度表达诱导了细胞周期蛋白依赖性激酶抑制剂1B（p27）的表达。重要的是，BCRC-3可以直接与miR-182- 5 p相互作用，随后作为miRNA海绵促进miR-182- 5 p靶向的p27的3 'UTR活性。此外，MJ显著增加BCRC-3的表达，导致p27的明显上调。BCRC-3作为肿瘤抑制剂通过miR-182- 5 p/p27轴抑制BC细胞增殖，有望成为BC治疗的新靶点。本文的在线版本（10.1186/s12943-018-0892-z）包含补充材料，可供授权用户使用。
Circular RNAs (circRNAs) are a new member of noncoding RNAs (ncRNAs) that have recently been described as key regulators of gene expression. Our previous study had identified the negative correlation between circHIPK3 and bladder cancer grade, invasion, as well as lymph node metastasis. However, the roles of circRNAs in cellular proliferation in bladder cancer remain largely unknown. We had analyzed circRNA high-throughout sequencing from human tissues and determined bladder cancer related circRNA-3 (BCRC-3, GenBank: KU921434.1) as a new candidate circRNA derived from PSMD1 gene. The expression levels of circRNAs, mRNAs and miRNAs in human tissues and cells were detected by quantitative real-time PCR (qRT-PCR). The effects of BCRC-3 on cancer cells were explored by transfecting with plasmids in vitro and in vivo. RNA pull down assay, luciferase reporter assay and fluorescence in situ hybridization were applied to verify the interaction between BCRC-3 and microRNAs. Anticancer effects of methyl jasmonate (MJ) were measured by flow cytometry assay, western blot and qRT-PCR. BCRC-3 was lowly expressed in bladder cancer tissues and cell lines. Proliferation of BC cells was suppressed by ectopic expression of BCRC-3 in vitro and in vivo. Mechanistically, overexpression of BCRC-3 induced the expression of cyclin-dependent kinase inhibitor 1B (p27). Importantly, BCRC-3 could directly interact with miR-182-5p, and subsequently act as a miRNA sponge to promote the miR-182-5p-targeted 3’UTR activity of p27. Furthermore, MJ significantly increased the expression of BCRC-3, resulting in an obvious up-regulation of p27. BCRC-3 functions as a tumor inhibitor to suppress BC cell proliferation through miR-182-5p/p27 axis, which would be a novel target for BC therapy. The online version of this article (10.1186/s12943-018-0892-z) contains supplementary material, which is available to authorized users.
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