环状 RNA 0005276 通过靶向 ADAM9 促进上皮性卵巢癌的发展。
Circ_0005276 aggravates the development of epithelial ovarian cancer by targeting ADAM9.
机构信息
Department of Gynecology, Binzhou Medical University Hospital, Binzhou, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 Oct;24(20):10375-10382. doi: 10.26355/eurrev_202010_23387.
OBJECTIVE
Our purpose was to assess the relationship between circ_0005276 and clinical features of epithelial ovarian cancer (EOC), and to illustrate the regulatory effect of circ_0005276 on migratory potential in EOC cells.
PATIENTS AND METHODS
EOC tissues and adjacent normal ones were collected from 49 EOC patients. Relative levels of circ_0005276 and ADAM9 in EOC tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between circ_0005276 and clinical features of EOC patients was analyzed. Moreover, migratory potentials of CAOV3 and SKOV3 cells affected by circ_0005276 were examined by transwell and wound healing assay. Regulatory effects of circ_0005276/ADAM9 feedback loop on the development of EOC were finally detected by Luciferase assay and rescue experiments.
RESULTS
It was found that circ_0005276 was upregulated in EOC tissues and its level was positively linked to rates of lymphatic metastasis and distant metastasis in EOC patients. Survival analysis showed worse OS and DFS in EOC patients expressing a high level of circ_0005276 than those with a low level. Besides, knockdown of circ_0005276 attenuated migratory potentials in EOC cells. ADAM9 was verified to be the target gene binding circ_0005276, and its level was positively regulated by circ_0005276. Notably, circ_0005276 aggravated the development of EOC by targeting ADAM9.
CONCLUSIONS
Circ_0005276 is highly expressed in EOC tissues, and its level is positively linked to metastasis. Serving as an unfavorable gene in the prognosis of EOC, circ_0005276 aggravates the development of EOC by upregulating ADAM9.
目的
本研究旨在评估环状 RNA（circRNA）circ_0005276 与上皮性卵巢癌（EOC）临床特征之间的关系，并阐明 circ_0005276 对 EOC 细胞迁移潜能的调节作用。
患者和方法
收集 49 名 EOC 患者的 EOC 组织和相邻正常组织。采用实时定量聚合酶链反应（qRT-PCR）检测 EOC 组织中 circ_0005276 和 ADAM9 的相对水平。分析 circ_0005276 与 EOC 患者临床特征的关系。此外，通过 Transwell 和划痕愈合实验检测 circ_0005276 对 CAOV3 和 SKOV3 细胞迁移能力的影响。最后通过荧光素酶报告基因检测和挽救实验检测 circ_0005276/ADAM9 反馈环对 EOC 发生发展的调控作用。
结果
研究发现，circ_0005276 在 EOC 组织中呈上调表达，其水平与 EOC 患者的淋巴转移率和远处转移率呈正相关。生存分析显示，circ_0005276 高表达的 EOC 患者的总生存期（OS）和无进展生存期（DFS）较低表达者更差。此外，circ_0005276 的敲低可减弱 EOC 细胞的迁移能力。ADAM9 被验证为结合 circ_0005276 的靶基因，其水平受 circ_0005276 正向调控。值得注意的是，circ_0005276 通过靶向 ADAM9 加重了 EOC 的发生发展。
结论
circ_0005276 在 EOC 组织中呈高表达，其水平与转移呈正相关。作为 EOC 预后不良的基因，circ_0005276 通过上调 ADAM9 加重了 EOC 的发生发展。
Zotero 插件