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Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
Published on: June 17, 2022
Systematic Analysis of E3 Ligase-Related Genes Identified UBE2L3 as a Prognostic Biomarker Associated With Drug
Chun Ling1,2, Nengneng Cao1, Huiping Wang1
1Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230000, People's Republic of China.
Background:
Acute Myeloid Leukemia (AML) is a prevalent neoplastic disorder. The roles of E3 ubiquitin ligases and related genes in AML drug resistance and prognosis remain unclear.
Methods:
Genes were identified from GeneCards and UniProt databases, differentially expressed genes were selected based on transcriptional sequencing data from wild-type and Adriamycin-resistant HL60 (HL60/WT & HL60/ADR) cell lines, and the intersection of these three sources was taken. We then constructed a prognostic model comprising five genes (HBP1, RNF130, RMND5B, TRIM32, and UBE2L3) through univariate Cox and LASSO regression analyses in the TCGA cohort and validated it in the BeatAML2.0 cohort. Finally, the expression of UBE2L3 was verified in cell lines and clinical case specimens.
Results:
The model accurately predicted AML prognosis and identified the UBE2L3 gene within the model as a high-risk biomarker associated with drug resistance, significantly influencing AML outcomes.
Conclusion:
The high expression of UBE2L3 is a reliable biomarker for drug resistance and poor prognosis of acute myeloid leukemia.
