Circular RNA expression pattern in cisplatin-resistant osteosarcoma cells

Jianhua Han, Zhiqiang Ye, Qinglei Kong, Feilong Wu, Gangwei Wang, Kun Wang


Background: 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.
Methods: 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).
Results: 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.
Conclusions: 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.