Xie Chen, Li Junyu, Xu Chen, Xiong Wenmin, Yuan Xia
Department of Radiotherapy, Jiangxi Cancer Hospital, Nanchang, China.
J Obstet Gynaecol Res. 2021 Mar;47(3):1068-1081. doi: 10.1111/jog.14639. Epub 2021 Jan 5.
Circular RNAs (circRNAs) are associated with tumorigenesis of breast cancer. Nevertheless, how and whether circRNA DNA methyltransferase 1 (circ-DNMT1) controls breast cancer development remains poorly understood.
The paired tumor and paracancer tissues (n = 41) were obtained from breast cancer patients. Circ-DNMT1, microRNA (miR)-485-3p, and zinc finger E-box binding homeobox 1 (ZEB1) abundances were measured by quantitative reverse transcription polymerase chain reaction and western blot. Cell colony formation, migration, invasion, and apoptosis were analyzed by colony formation analysis, transwell analysis, and flow cytometry. Target relationship was evaluated via dual-luciferase reporter analysis, RNA immunoprecipitation, and pull-down. The in vivo experiments were conducted using a xenograft model.
Circ-DNMT1 and ZEB1 levels were upregulated in breast cancer, and miR-485-3p was downregulated. Circ-DNMT1 knockdown restrained cell colony formation, migration, and invasion and increased apoptosis. MiR-485-3p was negatively regulated by circ-DNMT1, and miR-485-3p knockdown mitigated the effect of circ-DNMT1 silence on breast cancer development. ZEB1 was targeted via miR-485-3p, miR-485-3p overexpression repressed cell colony formation, migration, and invasion and triggered apoptosis by decreasing ZEB1. Circ-DNMT1 silence reduced ZEB1 expression via regulating miR-485-3p. Circ-DNMT1 knockdown reduced xenograft tumor growth.
Circ-DNMT1 knockdown constrains breast cancer development via modulating miR-485-3p/ZEB1 axis.
环状RNA（circRNAs）与乳腺癌的肿瘤发生有关。然而，circRNA DNA甲基转移酶1（circ-DNMT1）如何以及是否控制乳腺癌的发展仍知之甚少。
从乳腺癌患者中获取配对的肿瘤组织和癌旁组织（n = 41）。通过定量逆转录聚合酶链反应和蛋白质免疫印迹法检测circ-DNMT1、微小RNA（miR）-485-3p和锌指E盒结合同源盒1（ZEB1）的丰度。通过集落形成分析、Transwell分析和流式细胞术分析细胞集落形成、迁移、侵袭和凋亡。通过双荧光素酶报告基因分析、RNA免疫沉淀和下拉实验评估靶标关系。使用异种移植模型进行体内实验。
乳腺癌中circ-DNMT1和ZEB1水平上调，miR-485-3p水平下调。circ-DNMT1敲低抑制细胞集落形成、迁移和侵袭，并增加凋亡。miR-485-3p受circ-DNMT1负调控，miR-485-3p敲低减轻了circ-DNMT1沉默对乳腺癌发展的影响。ZEB1是miR-485-3p的靶标，miR-485-3p过表达通过降低ZEB1抑制细胞集落形成、迁移和侵袭并引发凋亡。circ-DNMT1沉默通过调节miR-485-3p降低ZEB1表达。circ-DNMT1敲低减少异种移植瘤的生长。
circ-DNMT1敲低通过调节miR-485-3p/ZEB1轴抑制乳腺癌发展。
