The Role Of ZNF622 Gene In Artesunate Anti-Leukemia And Its Mechanism

Objective: To investigate the role of ZNF622 in artesunate anti-leukemia and its specific molecular mechanism.Methods:(1)42 cases of acute myeloid leukemia,37 cases of acute lymphoblastic leukemia and 15 cases of chronic myeloid leukemia patients were the experimental group and 21 cases of non-hematological patients were the control group.The level of ZNF622 m RNA in bone marrow were detected by q PCR,and the level of ZNF622 proteins in bone marrow were detected by Western Blot.(2)After artesunate treated THP-1,Jurkat and K562 cells,CCK-8 assay was used to detect cell viability,flow cytometry was used to detect apoptosis,and western blot was used to detect the expression of ZNF622,STAT3,p-STAT3,BCL-2,and c-Myc proteins.(3)si RNA lentivirus silencing or overexpressed ZNF622 in THP-1 cells.Infection rate of cells was observed by fluorescence microscope and flow cytometry.The expression of ZNF622 and STAT3 m RNA were detected by q PCR,and the expression of ZNF622,STAT3,c-Myc proteins were detected by Western Blot.In STAT3 gene silenced THP-1 cell,the expression of STAT3 and ZNF622 m RNA were detected by q PCR,cell cycle was detected by flow cytometry,and the expression of STAT3,ZNF622,c-Myc proteins were detected by Western Blot.Finally,data were statistical analyzed.Results:(1)The m RNA and protein level of ZNF622 in AML,ALL and CML patients were lower than the control group(P<0.05);The expression of ZNF622 gene was negatively correlated with the risk degree of patients(P<0.05),and ZNF622 gene expression in M2,M5,T-ALL and B-ALL patients,were lower than in the control group(P<0.05).(2)Artesunate significantly inhibited the proliferation and promoted apoptosis of THP-1,Jurkat,K562 cells in a dose-dependent and time-dependent manner,and blocked cell cycle in G1 or S phase;Artesunate up-regulated the expression of ZNF622 in THP-1,Jurkat,K562 cells,down-regulated the expression of STAT3,p-STAT3,c-Myc proteins,down-regulated the BCL-2 protein expression in THP-1 and Jurkat cells,while up-regulated the BCL-2 protein expression in K562 cells(all P<0.05).(3)The expression of STAT3 in ZNF622 overexpression THP-1 cell were significantly lower than in the control group(P<0.05).The expression of STAT3 and c-Myc protein in ZNF622 silencing group were significantly higher than control group(P<0.05);Silencing STAT3 gene in THP-1 cell blocked cell cycle in G1 phase,increased ZNF622 protein expression,and decreased c-Myc expression.Conclusion: 1.Lower expression of ZNF622 gene was found in AML,ALL and CML patients,and the level of ZNF622 was negatively correlated with the risk degree of AL patients.2.Artesunate has an anti-leukemia effect,ZNF622,STAT3,c-Myc and BCL-2 may be involved in the anti-leukemia effect of artesunate,while the mechanism of BCL-2 may be different in AL and CML.3.ZNF622 can regulate STAT3 gene,and STAT3 may also can regulate ZNF622 in AML...