scholarly journals MicroRNA-335/ID4 dysregulation predicts clinical outcome and facilitates leukemogenesis by activating PI3K/Akt signaling pathway in acute myeloid leukemia

Aging ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 3376-3391 ◽  
Author(s):  
Jing-dong Zhou ◽  
Xi-xi Li ◽  
Ting-juan Zhang ◽  
Zi-jun Xu ◽  
Zhi-hui Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Outcome ◽  
Signaling Pathway ◽  
Myeloid Leukemia ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Acute Myeloid

scholarly journals Effects of Qinghuang Powder on Acute Myeloid Leukemia Based on Network Pharmacology, Molecular Docking, and In Vitro Experiments

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Ying-jian Zeng ◽  
Min Wu ◽  
Huan Zhang ◽  
Xin-ping Wu ◽  
Lu Zhou ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Target Genes ◽  
Akt Signaling ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Target Proteins ◽  
Qinghuang Powder ◽  
Acute Myeloid

Qinghuang powder (QHP) is a traditional Chinese herbal medicine. This is a unique formula that is frequently used to treat malignant hematological diseases such as acute myeloid leukemia (AML) in modern clinical practice. An approach of network pharmacology and experimental validation were applied to investigate the pharmacological mechanisms of QHP in AML treatment. First, public databases for target genes known to be associated with AML are searched and compared to the target genes of the active compounds in QHP. Second, AML-associated genes and QHP target genes are compared to identify overlapping enriched genes, and these were used to predict selected target genes that may be implicated in the effects of QHP on AML. Additionally, we conducted functional enrichment analyses, such as gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The significantly enriched pathway associated with potential target proteins was the PI3K-Akt signaling pathway, suggesting that these potential target proteins and pathways may mediate the beneficial biological effects of QHP on AML. All these following genes were found to occur in the compounds-target-pathway networks: AKT1, MAPK1, MAPK3, PIK3CG, CASP3, CASP9, TNF, TGFB1, MAPK8, and TP53. Then, based on the molecular docking studies, it was suggested that the active compound isovitexin can fit into the binding pockets of the top candidate QHP-AML target proteins (PIK3CG). Subsequently, based on the prediction by network pharmacology analysis, both in vitro AML cells and western blot experiments were performed to validate the curative role of QHP. QHP exerted its antitumor activity on AML in vitro, as it inhibits cells proliferation, reduced the expression of Bcl-2 protein, and downregulated the PI3K-Akt signaling pathway. In conclusion, these results revealed that QHP could treat AML via a “multicomponent, multitarget, multipathway” regulatory network. Furthermore, our study also demonstrated that the combination of network pharmacology with the experimental study is effective in discovering and identifying QHP in the treatment of AML and its underlying pharmacological mechanisms.

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