■复发/难治性急性髓系白血病(R/R-AML)由于化疗耐药而预后不良。环状RNA(circularRNAs,circRNAs)已经在包括血液恶性肿瘤在内的各种癌症的化疗耐药中显示出新兴的作用。然而,circRNAs在AML进展和耐药性中的潜在作用仍未确定.
■在这项研究中,在R/R-AML中分析循环circRNAs表达谱,使用人circRNA阵列从头AML和健康对照(HC)。进行生物信息学分析以探索差异表达的circRNAs(DE-circRNAs)。GO,KEGG通路分析,随着circRNA-miRNA-mRNA网络分析,进行鉴定涉及R/R-AML的潜在生物学途径。最后,UALCAN数据库用于评估不同靶DE-circRNAs相关mRNA的预后.
■48个DE-circRNAs被上调,而在R/R-AML样本中有27个DE-circRNAs下调。R/R-AML样品中上调的DE-circRNAs主要富集在细胞迁移的生物学过程和途径中,microRNAs在癌症中,Rap1和Ras信号通路。随机选择六个DE-circRNAs以进一步探索它们与R/R-AML的关系。6个候选DE-circRNAs相关靶mRNA的GO和KEGG通路分析主要参与信号转导和Ras信号通路的调控。通过将R/R-AML样品中差异表达基因(DEG)的RNA测序结果与候选DE-circRNAs预测的靶mRNA重叠,我们确定了68个重叠的靶向mRNA.使用UALCAN数据库分析,我们发现AML患者具有六个上调的DE-circRNA相关基因(ECE1,PI4K2A,SLC9A6,CCND3,PPP1R16B,和TRIM32)和一个下调的基因DE-circRNA相关基因(ARHGAP10)可能预后不良。
■这项研究揭示了R/R-AML中circRNAs的整体改变。DE-circRNAs及其相关基因可能被用作潜在的早期,用于AML诊断的敏感和稳定的生物标志物,R/R-AML监控,甚至作为R/R-AML的新治疗靶点。
UNASSIGNED: Relapsed/refractory acute myeloid leukemia (R/R-AML) has dismal prognosis due to chemotherapy resistance. Circular RNAs (circRNAs) have shown emerging roles in chemotherapy resistance in various cancers including hematologic malignancies. However, the potential roles of circRNAs in AML progression and drug resistance remain largely undetermined.
UNASSIGNED: In this study, circulating circRNAs expression profiles were analyzed among R/R-AML, de novo AML and healthy controls (HC) using a human circRNA Array. Bioinformatic analysis was carried out to explore the differentially expressed circRNAs (DE-circRNAs). GO, KEGG pathway analysis, along with circRNA-miRNA-mRNA network analysis, were conducted to identify the potential biological pathways involved in R/R-AML. Finally, the UALCAN database was used to assess the prognosis of different target DE-circRNAs-related mRNAs.
UNASSIGNED: Forty-eight DE-circRNAs were upregulated, whereas twenty-seven DE-circRNAs were downregulated in R/R-AML samples. Up-regulated DE-circRNAs in R/R-AML samples were mainly enrichment in the biological processes and pathways of cell migration, microRNAs in cancers, Rap1 and Ras signaling pathways. Six DE-circRNAs were randomly selected to further explore their relationships with R/R-AML. GO and KEGG pathway analyses of the six candidate DE-circRNAs-related target mRNAs were mainly involved in the regulation of signal transduction and Ras signaling pathway. By overlapping our RNA-sequencing results of differentially expressed genes (DEGs) in R/R-AML samples with the candidate DE-circRNAs-predicted target mRNAs, we identified sixty-eight overlapping targeted mRNAs. Using UALCAN database analysis, we identified that AML patients with six upregulated DE-circRNA-related genes (ECE1, PI4K2A, SLC9A6, CCND3, PPP1R16B, and TRIM32) and one downregulated gene DE-circRNA-related genes (ARHGAP10) might have a poor prognosis.
UNASSIGNED: This study revealed the overall alterations of circRNAs in R/R-AML. DE-circRNAs and their related genes might be used as potential early, sensitive and stable biomarkers for AML diagnosis, R/R-AML monitoring, and even as novel treatment targets for R/R-AML.