Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Department of Gynecology and Obstetrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Biomed Pharmacother. 2019 Oct;118:109311. doi: 10.1016/j.biopha.2019.109311. Epub 2019 Aug 10.
Circular RNAs (circRNAs) are a novel group of noncoding RNAs characterized by a covalently closed loop. An increasing evidence suggests that deregulated circRNAs exert their essential regulatory roles in oncogenesis. However, little is explored on the biological role of novel circRNAs in cervical cancer (CC) progression. In the present study, we analyzed two GSE microarrays to screen for CC-specific circRNAs and found two circRNAs both expressed in CC cells and tissues. Among them, circ_0005576 was significantly overexpressed in both CC tissues and cell lines. Furthermore, upregulated circ_0005576 was positively associated with advanced FIGO stage, lymph node metastasis, but was negatively related with overall survival of CC patients. Additionally, circ_0005576 knockdown induced a suppressed cell growth, colony formation and metastasis of HeLa and SiHa cells. Mechanistically, circ 0005576 was mainly located in the cytoplasm and served as a sponge of miR-153-3p to increase kinesin family member 20A (KIF20A) expression. Rescue assays further validated the effects of circ_0005576/miR-153-3p/KIF20A axis on CC proliferation, migration and invasion. In conclusion, our research reveals a novel circ_0005576/miR-153-3p/KIF20A axis promoting CC progression, which may suggest a new insight into the pathogenesis of CC.
环状 RNA（circRNAs）是一类新型的非编码 RNA，其特征是共价闭环。越来越多的证据表明，失调的 circRNAs 在肿瘤发生中发挥着重要的调节作用。然而，关于新型 circRNAs 在宫颈癌（CC）进展中的生物学作用，人们知之甚少。在本研究中，我们分析了两个 GSE 微阵列，以筛选 CC 特异性 circRNAs，并发现了两种在 CC 细胞和组织中均表达的 circRNAs。其中，circ_0005576 在 CC 组织和细胞系中均显著过表达。此外，上调的 circ_0005576 与 FIGO 晚期、淋巴结转移呈正相关，但与 CC 患者的总生存呈负相关。此外，circ_0005576 敲低可抑制 HeLa 和 SiHa 细胞的生长、集落形成和转移。机制上，circ0005576 主要位于细胞质中，并作为 miR-153-3p 的海绵，增加驱动蛋白家族成员 20A（KIF20A）的表达。挽救实验进一步验证了 circ_0005576/miR-153-3p/KIF20A 轴对 CC 增殖、迁移和侵袭的影响。总之，我们的研究揭示了一种新型的 circ_0005576/miR-153-3p/KIF20A 轴促进 CC 进展，这可能为 CC 的发病机制提供了新的见解。
