Han Jianhua, Ye Zhiqiang, Kong Qinglei, Wu Feilong, Wang Gangwei, Wang Kun
Department of Emergency, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
Department of Joint Replacement and Trauma Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
Transl Cancer Res. 2020 Jan;9(1):262-270. doi: 10.21037/tcr.2019.12.80.
Cisplatin resistance associated with circular RNA (circRNA) in osteosarcoma (OS) is not fully understood. The present study aimed to reveal the expression profile of circRNAs related to cisplatin resistance in OS.
Cisplatin-resistant OS cell lines (U2OS-R and MG63-R) were induced using different concentrations of cisplatin and RNA sequencing (RNA-seq) was performed to screen differentially expressed circRNAs in these cells. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the function of the differentially expressed circRNAs. The circRNAs identified by RNA-seq were randomly selected for expression identification by quantitative real-time polymerase chain reaction (qRT-PCR).
A total of 343 circRNAs were differentially expressed in U2OS-R cells compared with U2OS cells. Among these circRNAs, 253 were upregulated and 90 were downregulated. Analysis of the characteristics of the differentially expressed circRNAs showed that upregulated circRNAs were mainly distributed in chromosomes 1, 2, 3, 7, and 8, while downregulated circRNAs were distributed in all chromosomes except the X chromosome. GO and KEGG analyses revealed that the differentially expressed circRNAs were enriched in metabolic pathways, pathways in cancer, adherens junction, proteoglycans in cancer, and transcriptional misregulation in cancer pathway. Furthermore, three circRNAs (hsa_circ_0008336, hsa_circ_0004664, and hsa_circ_0003302) were upregulated in both U2OS-R and MG63-R cells.
Cisplatin-resistant cell lines showed a distinct circRNA expression profile. In particular, hsa_circ_0008336, hsa_circ_0004664, and hsa_circ_0003302 were upregulated in cisplatin-resistant cells and may be involved in the pathology of cisplatin resistance in OS.
骨肉瘤(OS)中与环状RNA(circRNA)相关的顺铂耐药性尚未完全明确。本研究旨在揭示骨肉瘤中与顺铂耐药相关的circRNA表达谱。
使用不同浓度的顺铂诱导顺铂耐药的骨肉瘤细胞系(U2OS-R和MG63-R),并进行RNA测序(RNA-seq)以筛选这些细胞中差异表达的circRNA。进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析以预测差异表达circRNA的功能。通过RNA-seq鉴定出的circRNA被随机选择用于通过定量实时聚合酶链反应(qRT-PCR)进行表达鉴定。
与U2OS细胞相比,U2OS-R细胞中共有343个circRNA差异表达。在这些circRNA中,253个上调,90个下调。对差异表达circRNA的特征分析表明,上调的circRNA主要分布在染色体1、2、3、7和8中,而下调的circRNA分布在除X染色体外的所有染色体中。GO和KEGG分析显示,差异表达的circRNA富集于代谢途径、癌症途径、黏着连接、癌症中的蛋白聚糖以及癌症途径中的转录失调。此外,三种circRNA(hsa_circ_0008336、hsa_circ_0004664和hsa_circ_0003302)在U2OS-R和MG63-R细胞中均上调。
顺铂耐药细胞系表现出独特的circRNA表达谱。特别是,hsa_circ_0008336、hsa_circ_0004664和hsa_circ_0003302在顺铂耐药细胞中上调,可能参与骨肉瘤顺铂耐药的病理过程。