Wu Han, Zhao Xibo, Wang Jing, Jiang Xinyan, Cheng Yan, He Yanan, Sun Liyuan, Zhang Guangmei
Department of Gynecology, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
Front Genet. 2022 Jan 26;12:815448. doi: 10.3389/fgene.2021.815448. eCollection 2021.
Cisplatin (CDDP) chemoresistance seriously affects the prognosis and survival of patients with ovarian cancer (OC). Previous research has shown that circular RNA CDR1as is biologically associated with a large number of cancers. However, the molecular mechanism underlying the role of CDR1as in CDDP chemoresistance in OC remains unclear. Here, we investigated the mechanism of CDR1as in CDDP-resistant OC. First, we employed bioinformatics analysis and quantitative real-time PCR (qRT-PCR) to determine the expression of CDR1as and related RNAs in CDDP-sensitive and -resistant OC tissues and cells. Then, functional experiments were used to determine cell proliferation, invasion, migration, and apoptosis in CDDP chemoresistance and parent OC cells . The effect of CDR1as in CDDP chemoresistance OC progression was tested in nude mice . Moreover, dual-luciferase assays and RNA immunoprecipitation (RIP) were performed to confirm the interactions of CDR1as and related RNAs. Finally, we used Western blotting to determine protein expression levels. Our findings interpret the underlying mechanisms of the CDR1as/miR-1299/PPP1R12B axis and shed light on the clinical applications for CDDP-chemoresistant OC.
顺铂(CDDP)耐药严重影响卵巢癌(OC)患者的预后和生存。先前的研究表明,环状RNA CDR1as与多种癌症存在生物学关联。然而,CDR1as在OC顺铂耐药中作用的分子机制仍不清楚。在此,我们研究了CDR1as在顺铂耐药OC中的作用机制。首先,我们采用生物信息学分析和定量实时PCR(qRT-PCR)来确定CDR1as和相关RNA在顺铂敏感和耐药OC组织及细胞中的表达。然后,通过功能实验来确定顺铂耐药和原代OC细胞中的细胞增殖、侵袭、迁移及凋亡情况。在裸鼠中测试了CDR1as在顺铂耐药OC进展中的作用。此外,进行了双荧光素酶测定和RNA免疫沉淀(RIP)以证实CDR1as与相关RNA的相互作用。最后,我们使用蛋白质印迹法来确定蛋白质表达水平。我们的研究结果阐释了CDR1as/miR-1299/PPP1R12B轴的潜在机制,并为顺铂耐药OC的临床应用提供了线索。