Expression And Function Of Long Noncoding RNA MIR22HG In Acute Myeloid Leukemia

Objective: LncRNA MIR22 HG plays a key role in the occurrence and development of d ifferent tumors,but the expression level and function of MIR22 HG in acute myeloid leukemia are still unclear.In this study,the expression of MIR22 HG and its downstream target genes and immune immune checkpoint genes in AML patients and its relationship with the survival of AML patients were analyzed.To preliminarily explore the molecular mechanism of MIR22 HG involved in regulating the development of AML,and provide new biomarkers and potential immunotherapy targets for AML patients.Methods: The expression of MIR22 HG in different types of blood tumors and normal hematopoietic cells was analyzed using bloodspot database;Kaplan-meier curve was used to analyze the relationship between MIR22 HG expression level and prognosis in TC GA-LAML and TCGA-OHSU datasets;C linical specimens were collected and the expression of MIR22 HG in newly AML patients and healthy controls was detected by RQ-PCR,and the relationship between MIR22 HG expression level and overall survival time(OS)of AML patients was analyzed;The correlation between MIR22 HG and its related downstream target genes and immune checkpoint genes in TCGA datasets and clinical specimens was analyzed.Finally,The expression of downstream target genes of MIR22 HG and immune checkpoint genes in AML patients were detected by RQ-PCR and the relationship between their expression and OS in AML patients was analyzed.Results: The expression of MIR22 HG gene in AML tumor cells was significantly higher than that in normal human hematopoietic cells;The survival analysis results showed that AML patients with high expression of MIR22 HG had poor prognosis in both TCGA-LAML and TCGA-OHSU data sets(P=0.0170;P=0.0082);The results of RQ-PCR showed that the expression level of MIR22 HG in the newly diagnosed AML patients was significantly higher than that in the healthy controls(P=0.0059),and the high expression of MIR22 HG had a poor prognosis(P=0.0440);In TCGA database,the correlation analysis results showed that MIR22 HG was positively correlated with its downstream target genes NCOR2,CDKN1 A and SFRP2(rs=0.18;rs=0.43;rs=0.12),and negatively correlated with MYC,HMGB1,SMAD2,SMAD4 and DAPK1(rs=-0.48;rs=-0.24;rs=-0.26;rs=-0.40;rs=-0.14);The results of RQ-PCR showed that the expression levels of HMGB1,NCOR2 and SFRP2 in newly AML patients were significantly higher than those in the healthy controls(P<0.001).Only HMGB1 had a significant positive correlation with MIR22HG(rs=0.48),and the OS of AML patients with high expression of HMGB1 was lower than that of low expression patients(P=00027);The OS of AML patients with high expression of C LTA4 and PDL2 from TCGA-LAML and our clinical samples were lower than that of low expression patients(P<0.05);And the correlation analysis results showed that MIR22 HG and HMGB1 had a significant positive correlation with immune checkpoint gene CTLA4 in TCGA database and our clinical samples.Conclusion: The expression of MIR22 HG was upregulated in AML patients,and the prognosis of AML patients with high expression of MIR22 HG was poor.And the mechanism may be through regulation of downstream target gene HMGB1 to mediate the occurrence and development of AML,And HMGB1 was also found to be correlated with CTLA4,suggesting that MIR22 HG may be a novel biomarker and a potential immunotherapy target for AML.