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circ_0067934 过表达通过 miR-545/EIF3C 轴作为癌基因促进宫颈癌进展。

Overexpressed circ_0067934 acts as an oncogene to facilitate cervical cancer progression via the miR-545/EIF3C axis.

机构信息

Department of Gynaecology and Obstetrics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

Department of Pharmacology and Toxicology, Wright State University, Fairborn, Ohio.

出版信息

J Cell Physiol. 2019 Jun;234(6):9225-9232. doi: 10.1002/jcp.27601. Epub 2018 Oct 26.

Abstract

Circular RNAs were recently identified as a novel type of noncoding RNAs. An increasing number of reports have demonstrated their essential regulatory roles in various biological processes and human diseases, including cancer. However, the role of circRNA in cervical cancer (CC) remains largely unknown. In the current study, we investigated the physiological functions of circ_0067934 during CC development and progression. We found that circ_0067934 was overexpressed in CC tissues and cell lines. Circ_0067934 upregulation was associated with advanced stage, lymph node metastasis, and poor prognosis in CC patients. Knockdown of circ_0067934 suppressed the proliferation, colony formation, migration, invasion, and epithelial-mesenchymal transition of CC cells in vitro. Circ_0067934 loss also inhibited CC tumor growth in vivo. Mechanistically, silencing circ_0067934 increased miR-545 expression. MiR-545 repressed EIF3C expression through targeting its 3'-untranslated region. MiR-545 suppressed the proliferation, migration, and invasion of CC cells, whereas restoration of EIF3C could rescue the effects of circ_0067934 knockdown. Taken together, our findings revealed that circ_0067934 promotes CC progression via miR-545/EIF3C axis. Our study may provide a new insight into the pathogenesis of CC.

摘要

环状 RNA 最近被鉴定为一种新型的非编码 RNA。越来越多的报道表明,它们在各种生物过程和人类疾病中(包括癌症)发挥着重要的调节作用。然而,环状 RNA 在宫颈癌(CC)中的作用在很大程度上仍然未知。在本研究中,我们研究了 circ_0067934 在 CC 发展和进展过程中的生理功能。我们发现 circ_0067934 在 CC 组织和细胞系中过度表达。circ_0067934 的上调与 CC 患者的晚期、淋巴结转移和不良预后相关。circ_0067934 的敲低抑制了 CC 细胞在体外的增殖、集落形成、迁移、侵袭和上皮-间充质转化。circ_0067934 的缺失也抑制了 CC 肿瘤在体内的生长。机制上,沉默 circ_0067934 增加了 miR-545 的表达。miR-545 通过靶向其 3'-非翻译区来抑制 EIF3C 的表达。miR-545 抑制了 CC 细胞的增殖、迁移和侵袭,而 EIF3C 的恢复可以挽救 circ_0067934 敲低的作用。综上所述,我们的研究结果表明,circ_0067934 通过 miR-545/EIF3C 轴促进 CC 的进展。我们的研究可能为 CC 的发病机制提供新的见解。

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