Expression Profile Screening and Bioinformatics Analysis of circRNA, LncRNA, and mRNA in Acute Myeloid Leukemia DrugResistant CellsMeiling Li1, Fuxue Meng3, Quanyi Lu21Zhongshan Hospital Affiliated to Xiamen University, Department of Hematology, Xiamen, China; The Third Affiliated Hospital of Guizhou Medical University, Department of Hematology and Rheumatology, Duyun, China
2Zhongshan Hospital Affiliated to Xiamen University, Department of Hematology, Xiamen, China
3The Third Affiliated Hospital of Guizhou Medical University, Department of Hematology and Rheumatology, Duyun, China
Objective: Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy, and drug resistance and relapse are key factors in the failure of leukemia treatment. Studies have increasingly shown that circRNA and LncRNA play important roles in the development of tumors, but their roles remain unclear in the mechanism of AML resistance.
Materials and Methods: Resistant AML cell line HL-60/ADM (adriamycin, ADM) was constructed and circRNA, LncRNA, and mRNA expression profiles were screened followed by high-throughput sequencing. Bioinformatics analysis was then carried out, and the circRNA-miRNA ceRNA network was constructed and confirmed using qRT-PCR analysis.
Results: A total of 1824 circRNAs, 2414 LncRNAs, and 5346 mRNAs were screened for differentially expressed genes. Enrichment analysis was performed utilizing Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes, which mainly involved protein domain specific binding, transforming growth factor-β (TGF-β) receptor, and cellular metabolism. The mTOR signaling pathway, MAPK signaling pathway, RAP1 signaling pathway, and Akt signaling pathway were closely related to drug resistance.
Conclusion: Our study provides a systematic outlook on the potential function of ncRNA in the molecular mechanisms of resistant AML cells. Hsa-circ-0000978 and hsa-circ-0000483 might serve as potential prognostic biomarkers and therapeutic targets of AML resistance.
Keywords: Acute myeloid leukemia, Drug resistance, CircRNA, LncRNA, Bioinformatics analysis
Akut Myeloid Lösemi İlaç-Dirençli Hücrelerde circRNA, LncRNA, ve mRNA Ekspresyon Profili Tarama ve Biyoinformatik AnaliziMeiling Li1, Fuxue Meng3, Quanyi Lu21Zhongshan Hospital Affiliated to Xiamen University, Department of Hematology, Xiamen, China; The Third Affiliated Hospital of Guizhou Medical University, Department of Hematology and Rheumatology, Duyun, China
2Zhongshan Hospital Affiliated to Xiamen University, Department of Hematology, Xiamen, China
3The Third Affiliated Hospital of Guizhou Medical University, Department of Hematology and Rheumatology, Duyun, China
Amaç: Akut myeloid lösemi (AML) oldukça heterojen bir hematolojik malignitedir, ve tedavi başarısızlığında ilaç direnci ve nüks anahtar rol oynamaktadır. Çalışmalar, circRNA ve lncRNA’nın tümör gelişiminde önemli rol oynadığını artarak göstermektedir, ancak AML direnç mekanizmasında rolleri belirsizliğini korumaktadır.
Gereç ve Yöntem: Dirençli AML hücre hattı HL-60/ADM (adriamisin, ADM) oluşturuldu ve circRNA, LncRNA, ve mRNA ekspresyon profilleri yüksek-kapasitede dizileme sonrası tarandı. Sonra biyoinformatik analiz gerçekleştirildi ve circRNA-miRNA ceRNA ağı oluşturuldu ve qRT-PCR analizi kullanılarak doğrulandı.
Bulgular: Farklı ifade edilen genler için toplam 1824 circRNA, 2414 LncRNA, ve 5346 mRNA tarandı. Başlıca protein domain spesifik bağlama, transforme edici büyüme faktörü-β (TGF-β) reseptörü, ve hücresel metabolizma ile ilgili ‘Gene Ontology’ ve ‘Kyoto Encyclopedia of Genes and Genome’ kullanılarak zenginleştirme analizi gerçekleştirildi. mTOR sinyal yolağı, MAPK sinyal yolağı, RAP1 sinyal yolağı ve Akt sinyal yolağı ilaç direnci ile yakından ilişkili idi.
Sonuç: Çalışmamız, dirençli AML hücrelerinin moleküler mekanizmasında ncRNA’ın potansiyel fonksiyonuna sistematik bir bakış açısı sağlamıştır. Hsa-circ-0000978 ve hsa-circ-0000483 potansiyel prognostik biyogöstergeler ve AML direncinin terapötik hedefleri olarak işlev görebilirler.
Anahtar Kelimeler: Akut myeloid lösemi, İlaç direnci, CircRNA, LncRNA, Biyoinformatik analiz
Meiling Li, Fuxue Meng, Quanyi Lu. Expression Profile Screening and Bioinformatics Analysis of circRNA, LncRNA, and mRNA in Acute Myeloid Leukemia DrugResistant Cells. Turk J Hematol. 2020; 37(2): 104-110
Corresponding Author: Quanyi Lu, China |
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