Circular RNA hsa_circ_0000263 participates in cervical cancer development by regulating target gene of miR-150-5p
Circular RNA hsa_circ_0000263 participates in cervical cancer development by regulating target gene of miR-150-5p
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DOI：
10.1002/jcp.27796
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Wu, Xufeng
中科院分区：
文献类型：
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作者：
Cai, Hongning;Zhang, Peng;Wu, Xufeng
环状RNA （circRNA）是一类新的非编码RNA，在许多病理过程中起着重要作用。宫颈癌是最常见的妇科恶性肿瘤。近年来的研究表明，有多种circRNA参与了宫颈癌的发病过程。采用实时荧光定量聚合酶链反应技术，从GSE102686中筛选出高表达的hsa_circ_0000263。在本研究中，我们在体外和体内研究了hsa_circ_0000263是否可能影响宫颈癌细胞的增殖、迁移、细胞周期和凋亡。荧光素酶报告基因实验和RNA免疫沉淀实验证实了miR-150-5p与hsa_circ_0000263之间的直接相互作用。通过western blot和免疫组化，我们证实hsa_circ_0000263可以通过影响miR-150-5p调节小鼠双分钟4 （MDM4）的表达，最终影响p53基因的表达。我们发现hsa_circ_0000263在宫颈癌细胞中显著上调。此外，hsa_circ_0000263基因的敲低会抑制细胞的增殖和迁移能力。总之，我们目前的研究揭示了hsa_circ_0000263/miR-150-5p/MDM4/p53调控网络在宫颈癌中的重要作用，为宫颈癌的发病机制提供了新的认识。
Circular RNA (circRNA) is a new class of noncoding RNA, and plays an important role in many pathological processes. Cervical cancer is the most common gynecologic malignant tumor. Recently, studies have shown that there is a variety of circRNA involved in the pathogenesis of cervical cancer. We screened out the highly expressed hsa_circ_0000263 from GSE102686 by the quantitative real-time polymerase chain reaction assay in cervical cancer cell lines. In this study, we investigated whether hsa_circ_0000263 might affect cell proliferation, migration, cell cycle and apoptosis in cervical cancer in vitro and in vivo. The luciferase reporter assay and RNA immunoprecipitation assay confirmed the direct interaction between miR-150-5p and hsa_circ_0000263. By using western blot and immunohistochemistry, we confirmed that hsa_circ_0000263 can regulate the expression of murine double minute 4 (MDM4) by affecting miR-150-5p, and finally affect the expression of p53 gene. We found that hsa_circ_0000263 was significantly upregulated in cervical cancer cells. In addition, the knockdown of hsa_circ_0000263, would inhibit cell proliferation and migration ability. In conclusion, our current research reveals the important role of hsa_circ_0000263/miR-150-5p/MDM4/p53 regulatory network in cervical cancer and provides a new insight into the pathogenesis of cervical cancer.