Hsa_circ_0074269-mediated Upregulation of TUFT1 Through miR-485-5p Increases Cisplatin Resistance in Cervical Cancer

顺铂 宫颈癌 细胞凋亡 基因沉默 癌症研究 微泡 下调和上调 小RNA 体内 癌症 细胞生长 癌细胞 体外 化学 医学 分子生物学 生物 内科学 化疗 基因 生物化学 生物技术
作者
Jing Chen,Sheng Wu,Jue Wang,Yu Sha,Yong Ji
出处
期刊:Reproductive Sciences [Springer Nature]
卷期号:29 (8): 2236-2250 被引量:11
标识
DOI:10.1007/s43032-022-00855-9
摘要

Most cervical cancer patients are prone to developing acquired cisplatin (DDP) resistance. Hsa_circ_0074269 (circ_0074269) plays a promoting role in cervical cancer, but whether circ_0074269 mediates cervical cancer resistance to DDP is unclear. Expression of circ_0074269 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The half-maximal inhibitory concentration (IC50) value, viability, proliferation, colony formation, migration, and apoptosis of DDP-resistant cervical cancer cells were determined. The molecular mechanisms associated with circ_0074269 were predicted by bioinformatics analysis and confirmed by dual-luciferase reporter and RIP assays. Xenograft assay was conducted to validate the effect of circ_0074269 on DDP resistance in vivo. Exosomes were isolated by ultracentrifugation. Circ_0074269 was overexpressed in DDP-resistant cervical cancer samples and cells. Silencing of circ_0074269 elevated DDP sensitivity, repressed DDP-resistant cervical cancer cell proliferation, and induced DDP-resistant cervical cancer cell apoptosis in vivo and in vitro and curbed DDP-resistant cervical cancer cell migration in vitro. And circ_0074269 could regulate DDP resistance via regulating TUFT1 expression via sponging miR-485-5p. More strikingly, circ_0074269 was also overexpressed in exosomes from DDP-resistant cervical cancer cells, and circ_0074269 could be delivered via exosomes. Circ_0074269 facilitated DDP resistance via elevating TUFT1 expression via sponging miR-485-5p, proving novel evidence to offer circ_0074269 as a target for cervical cancer treatment.
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