Bioinformatic analysis of the expression profile and identification of RhoGDI2 as a biomarker in imatinib-resistant K562 cells

被引:2
作者
Yang, Yulin [1 ,2 ]
Zhong, Fangmin [1 ]
Jiang, Junyao [1 ]
Li, Meiyong [1 ]
Yao, Fangyi [1 ]
Liu, Jing [1 ]
Cheng, Ying [1 ,2 ]
Xu, Shuai [1 ,2 ]
Chen, Song [1 ,2 ]
Zhang, Haibin [1 ]
Xu, Yanmei [1 ]
Huang, Bo [1 ]
机构
[1] Nanchang Univ, Affiliated Hosp 2, Jiangxi Prov Clin Res Ctr Lab Med, Dept Clin Lab,Jiangxi Prov Key Lab Lab Med, Nanchang, Peoples R China
[2] Nanchang Univ, Sch Publ Hlth, Nanchang, Peoples R China
关键词
CML; imatinib resistant; pathway enrichment analyses; PPI; miRNA-mRNA network; biomarker; RHoGDI(2); K562; MEDIATED DRUG-RESISTANCE; ARHGDIB; ABL; METASTASIS; INHIBITOR; APOPTOSIS; THERAPY; GENES;
D O I
10.1080/16078454.2023.2244856
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives Chronic myeloid leukemia (CML) is an aggressive malignancy originating from hematopoietic stem cells. Imatinib (IM), the first-generation tyrosine kinase inhibitor, has greatly improved theliving quality of CML patients. However, owing to the recurrence and treatment failure coming from tyrosine kinase inhibitor (TKIs) resistance, some CML patients still bear poor prognosis. Therefore, we aimed to seek potential signaling pathways and specific biomarkers for imatinib resistance. Methods We performed mRNA and miRNA expression profiling in imatinib-sensitive K562 cells (IS-K562) and imatinib-resistant K562 cells (IR-K562). Differentially expressed genes (DEGs) were identified and pathway enrichment analyses were performed to explore the potential mechanism. The protein-protein interaction (PPI) network and miRNA-mRNA regulatory network were constructed to explore potential relationships among these genes. RT-qPCR, western blot and CCK8 were used for further experiments. Results A total of 623 DEGs and 61 differentially expressed miRNAs were identified. GO revealed that DEGs were mainly involved in cell adhesion, cell migration, differentiation, and inflammatory response. KEGG revealed that DEGs were typically enriched in the Rap1 signaling pathway, focal adhesion, proteoglycans and transcriptional misregulation in cancer, signaling pathways regulating pluripotency of stem cells and some immune-related pathways. The protein-protein interaction (PPI) network and miRNA-mRNA regulatory network revealed a web of diverse connections among genes. Finally, we proved that RHoGDI(2) played a critical role in imatinib resistance. Conclusion The dynamic interplay between genes and signaling pathways is associated with TKIs resistance and RHoGDI(2) is identified as a biomarker in IR-K562.
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页数:11
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