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环状RNA Cdr1as通过抑制miR-1270上调SCAI以抑制卵巢癌顺铂耐药性。

Circular RNA Cdr1as Upregulates SCAI to Suppress Cisplatin Resistance in Ovarian Cancer via miR-1270 Suppression.

作者信息

Zhao Zhao, Ji Mei, Wang Qianqing, He Nannan, Li Yue

机构信息

Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

出版信息

Mol Ther Nucleic Acids. 2019 Dec 6;18:24-33. doi: 10.1016/j.omtn.2019.07.012. Epub 2019 Jul 29.

Abstract

The aim of this study is to explore the roles of circular RNA (circRNA) Cdr1as on cisplatin resistance in ovarian cancer and explore the underlying mechanisms. We investigated the expression of circRNAs in five paired cisplatin-sensitive and cisplatin-resistant tissues of ovarian cancer by microarray analysis. The quantitative real-time PCR analysis was to investigate the expression pattern of Cdr1as in cisplatin-resistant ovarian cancer patient tissues and cell lines. Then, the effects of Cdr1as on cisplatin resistance, cell proliferation, and apoptosis were assessed in ovarian cancer cells. In this study, Cdr1as was observed to be downregulated in cisplatin-resistant patient tissues and cell lines. Overexpression of Cdr1as inhibited cell proliferation and promoted the cisplatin-induced cell apoptosis in ovarian cancer cells. Then we demonstrated that repressed Cdr1as promoted the miR-1270 expression, and miR-1270 could bind to the predicted binding site of Cdr1as. Furthermore, we found that miR-1270 displayed its role via modulating the Suppressor of Cancer Cell Invasion (SCAI) expression. Importantly, we demonstrated that Cdr1as was downregulated in serum exosomes from cisplatin-resistant patients. In summary, our study demonstrated that Cdr1as sensitizes ovarian cancer to cisplatin by regulating the miR-1270/SCAI signaling pathway.

摘要

本研究旨在探讨环状RNA(circRNA)Cdr1as在卵巢癌顺铂耐药中的作用,并探究其潜在机制。我们通过微阵列分析研究了五对卵巢癌顺铂敏感和耐药组织中circRNAs的表达情况。定量实时PCR分析用于研究Cdr1as在顺铂耐药卵巢癌患者组织和细胞系中的表达模式。随后,评估了Cdr1as对卵巢癌细胞顺铂耐药性、细胞增殖和凋亡的影响。在本研究中,观察到Cdr1as在顺铂耐药患者组织和细胞系中表达下调。Cdr1as的过表达抑制了卵巢癌细胞的增殖,并促进了顺铂诱导的细胞凋亡。然后我们证明,Cdr1as表达受抑制会促进miR-1270的表达,且miR-1270可与Cdr1as的预测结合位点结合。此外,我们发现miR-1270通过调节癌细胞侵袭抑制因子(SCAI)的表达发挥作用。重要的是,我们证明了Cdr1as在顺铂耐药患者血清外泌体中表达下调。总之,我们的研究表明,Cdr1as通过调节miR-1270/SCAI信号通路使卵巢癌对顺铂敏感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7ba/6726918/e867196e1b79/gr1.jpg

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