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circPVT1 过表达通过调节 ABCB1 促进骨肉瘤细胞对阿霉素和顺铂的耐药性,circPVT1 是一种有潜力的新型环状 RNA 生物标志物。

Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1.

机构信息

Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, PR China.

Institute of Bone Tumor Affiliated to Tongji University, School of Medicine, Shanghai 200072, PR China.

出版信息

Int J Biol Sci. 2018 Feb 12;14(3):321-330. doi: 10.7150/ijbs.24360. eCollection 2018.

Abstract

Circular RNAs (circRNAs) represent a widespread class of non-coding RNAs generated from back-splicing, with a circular loop structure. Many circRNAs have been reported to play essential roles in cancer development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNA in osteosarcoma (OS) remains largely unknown. In the current study, we examined the expression level of circular RNA PVT1 (circPVT1), previously screened and identified the oncogenic role in gastric cancer, in OS and found that circPVT1 was significantly up-regulated in the OS tissues, serums and chemoresistant cell lines, correlated with poor prognosis of OS patients. Besides, ROC curve demonstrated that circPVT1 may be a better diagnostic biomarker than alkaline phosphatase (ALP) in OS with more sensitivity and specificity. In addition, functional assays revealed that circPVT1 knockdown by siRNA could weaken the resistance to doxorubicin and cisplatin of OS cells through decreasing the expression of classical drug resistance-related gene ABCB1. These findings may provide a new insight into the role of circPVT1 as a biomarker for the diagnosis and treatment target of OS.

摘要

环状 RNA(circRNAs)是一类通过反向剪接形成的具有环状结构的非编码 RNA。许多 circRNAs 已被报道在癌症发展中发挥重要作用,并有可能成为临床诊断的新型生物标志物。然而,circRNA 在骨肉瘤(OS)中的作用仍知之甚少。在本研究中,我们检测了先前筛选并鉴定在胃癌中具有致癌作用的环状 RNA PVT1(circPVT1)在 OS 中的表达水平,发现 circPVT1 在 OS 组织、血清和耐药细胞系中显著上调,与 OS 患者的预后不良相关。此外,ROC 曲线表明,circPVT1 可能是一种比碱性磷酸酶(ALP)更好的 OS 诊断生物标志物,具有更高的敏感性和特异性。此外,功能分析表明,通过 siRNA 敲低 circPVT1 可通过降低经典耐药相关基因 ABCB1 的表达来减弱 OS 细胞对阿霉素和顺铂的耐药性。这些发现可能为 circPVT1 作为 OS 诊断和治疗靶点的生物标志物提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/063b/5859477/bbf450a59a72/ijbsv14p0321g001.jpg

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