Wu Xinyu, Liu Daoyan, Wang Shuzhen, Liu Jie
Department of Laboratory Medicine, The Affiliated Maternity and Child Health Care Hospital, Xuzhou Medical University, Xuzhou 221009, People's Republic of China.
Onco Targets Ther. 2021 Jan 7;14:97-110. doi: 10.2147/OTT.S266186. eCollection 2021.
Some circular RNAs have been found to be effective therapeutic targets for OC. However, the biological function of circ_0007444 in OC is still unknown. Thus, this study investigated the role of circ_0007444 in OC progression.
circ_0007444 expression was monitored in 87 OC patients and OC cells by quantitative real-time polymerase chain reaction. An in vitro study was performed to research the biological function of circ_0007444, including cell counting kit-8 assay, flow cytometry, wound healing assay, and transwell experiment. Luciferase reporter gene assay and RNA immunoprecipitation assay were used to reveal the interaction between circ_0007444, miR-570-3p, and PTEN. PTEN protein expression was determined by Western blot. In vivo study was performed using nude mice. Ki67, PTEN expression, and apoptosis in xenograft tumors was respectively researched by immunohistochemistry and Tunel assay.
circ_0007444 was down-regulated in 87 OC patients, which was related to advanced tumor stage and grade, large tumor size, and low 60-month percent survival (<0.05 or <0.01). circ_0007444 inhibited proliferation, migration, and invasion, and promoted apoptosis of OC cells (<0.01). circ_0007444 promoted PTEN expression via sponging miR-570-3p. miR-570-3p up-regulation and PTEN down-regulation reversed the inhibitory effect of circ_0007444 on OC cells malignant phenotype (<0.01). circ_0007444 inhibited OC growth in vivo. In xenograft tumor, circ_0007444 decreased Ki67 expression but increased PTEN expression and apoptosis.
circ_0007444 is a tumor suppressor in OC, which inhibits OC progression by mediating the miR-570-3p/PTEN. circ_0007444 can be a potential candidate for targeted therapy of OC.
已发现一些环状RNA是卵巢癌（OC）有效的治疗靶点。然而，circ_0007444在OC中的生物学功能仍不清楚。因此，本研究探讨了circ_0007444在OC进展中的作用。
通过定量实时聚合酶链反应监测87例OC患者和OC细胞中circ_0007444的表达。进行体外研究以探究circ_0007444的生物学功能，包括细胞计数试剂盒-8检测、流式细胞术、伤口愈合检测和Transwell实验。荧光素酶报告基因检测和RNA免疫沉淀检测用于揭示circ_0007444、miR-570-3p和PTEN之间的相互作用。通过蛋白质免疫印迹法测定PTEN蛋白表达。使用裸鼠进行体内研究。通过免疫组织化学和Tunel检测分别研究异种移植瘤中的Ki67、PTEN表达和细胞凋亡情况。
87例OC患者中circ_0007444表达下调，这与肿瘤晚期、高分级、肿瘤体积大及60个月生存率低相关（<0.05或<0.01）。circ_0007444抑制OC细胞的增殖、迁移和侵袭，并促进其凋亡（<0.01）。circ_0007444通过吸附miR-570-3p促进PTEN表达。miR-570-3p上调和PTEN下调可逆转circ_0007444对OC细胞恶性表型的抑制作用（<0.01）。circ_0007444在体内抑制OC生长。在异种移植瘤中，circ_0007444降低Ki67表达，但增加PTEN表达和细胞凋亡。
circ_0007444是OC中的一种肿瘤抑制因子，其通过介导miR-570-3p/PTEN抑制OC进展。circ_0007444可能是OC靶向治疗的潜在候选物。
