| Objective:Acute myeloid leukemia(AML)is a familiar type of acute leukemia with high recurrence rate and mortality.However,AML screening and disease assessment methods are single and lack of standardization,which cannot meet the needs of clinical diagnosis and treatment.In addition,the regulatory mechanism of AML pathogenesis has not been elucidated.This study detected abnormal expression of lncRNA XLOC?109948 in 113 AML patients,and explored the underlying mechanisms of XLOC?109948 regulating proliferation,apoptosis and autophagy of AML cells.It is of great significance for screening AML patients and evaluating disease progression.Methods:1.A total of 113 AML patients and 30 controls came from The Second Affiliated Hospital of Kunming Medical University.Collecting their Bone marrow tissues and peripheral blood,then lncRNA XLOC?109948 was detected by RT-qPCR and the the effect of XLOC?109948 on clinicopathologic factors was assessed;2.OCI-AML3 cell line was transfected by lentivirus.After knocking down and overexpress XLOC?109948,using CCK-8,Annexin V/PI to observe whether XLOC 109948 would affect these the biological phenotype of tumor cells;3.The autophagy level of OCI-AML3 cell and related proteins of the PI3K-Akt signaling pathway was assessed using RT-qPCR and Western bolt.Results:1.The expression of lncRNA XLOC?109948 in bone marrow and serum of AML patients and AML patients with complete remission(AML-CR)were higher than healthy people(p<0.001).When the expression of XLOC?109948 in the bone marrow increased,the expression in the serum also increased,and the results of disease progression monitoring results of the two types of samples were consistent(r2=0.7585,p<0.001),indicating that the serum samples could replace the bone marrow samples in some degree.The expression of XLOC?109948 was significantly decreased when patients with AML reached to CR,and significantly increased when patients recurrent(p<0.05).The results showed that area under the curve value was 0.898(p<0.001,95%CI:0.847?0.948),which suggested the XLOC?109948 expression level might be a potential biomarker in discriminating AML from controls.XLOC?109948 expression significantly correlated with clinicopathologic parameters of cytogenetics(p<0.05).but there was no statistically significant difference between gender,age,WBC Blast,FAB classification and other clinical characteristics(p>0.05).2.In vitro,after knocking down lncRNA XLOC?109948 in OCI-AML3 cells detected CCK-8 at 450nm,show that the absorbance of the knockdown group was lower than the overexpressed group(p<0.001).XLOC?109948 downregulation reduced cell increased apoptosis(p<0.001).XLOC?109948 knockdown inhibited the levels of LC3?/?(p<0.01),enhanced the levels of p62(p<0.001).3.RT-qPCR and western bolt results showed that the expression levels of Akt and PI3K in the experimental group become no significant change compared with the control group(p>0.05),while the expression of p-Akt(p<0.01)and p-PI3k proteins(p<0.001)is decreased in overexpressed group.Conclusions:1.lncRNA XLOC?109948 is an oncogene,and it is overexpressed in AML patients,and its expression is closely related to the disease process and AML cytogenetics.2.XLOC?109948 expression was transferred from bone marrow to blood with the progression of AML.The expression of XLOC?109948 in bone marrow was positively correlated with the expression in serum.Serum samples are better than bone marrow samples in clinical diagnosis and treatment.and it also suggests that serum samples can replace bone marrow samples.3.The ROC curve suggested that XLOC?109948 could be a potential diagnostic indicator for AML,but its specific diagnostic value still needs to be included in more clinical samples.4.When overexpress XLOC?109948,the leveal of proliferation and autophagy raised.apoptosis decreased.5.XLOC?109948 molecular mechanism investigates suggested that it can regulate PI3K-Akt signaling pathway and change the AML development progression in vivo. |
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