The Study Of The Expression Level And Function Of Long-non-coding RNA Pandar In Acute And Chronic Myeloid Leukemia

Objective:Abundant studies have shown that lncRNA PANDAR plays an oncogenic role in human solid tumors.Although abnormal expression of PANDAR has been well investigated in solid tumors,it was rarely studied in hematologic diseases.Hence,this study aims to explore the expression level and its clinical significance of LncRNA PANDAR in patients who are diagnosed with AML and CML and make further explorations of its potential functional mechanism.Methods:For detecting the expression level of PANDAR in 119 AML patients,68 CML patients and 26 controls,real-time quantitative PCR（RQ-qPCR）was used in this study.The prognostic values were evaluated by using Kaplan–Meier analysis,Cox regression analyses and Logistic regression analysis.The cell line with high expression of PANDAR（THP-1）was screened for functional study.SiRNA was used to silence the expression of PANDAR in leukemia cell THP-1.Cell proliferation and apoptosis of cell with Si-THP-1 and Si-NC were respectively detected by cell counting and flow cytometry.The prediction of the downstream gene of PANDAR was carried out by reading a large number of literatures and bioinformatic analysis.And the relationship between PANDAR and acute myeloid leukemia was further explored.Results:1.PANDAR was significantly over-expressed in AML compared with normal samples（P<0.001）.Patients with high-expression of PANDAR(PANDAR^high)were older and showed higher bone marrow（BM）blast than patients in PANDAR^low group（P=0.029 and P=0.032,respectively）.Significant differences between these groups were also detected regarding risk group and karyotype finding（P=0.009 and 0.041,respectively）.Importantly,PANDAR^highigh patients presented a significant lower complete remission（CR）rate compared to PANDAR^lowow patients（P<0.001）.Furthermore,Kaplan-Meier analysis showed that PANDAR^high patients had shorter overall survival（OS）compared to PANDAR^low patients observing the whole AML cohort,and also in the non-M3 group of patients（P<0.001 and=0.005,respectively）.Multivariate analysis of Cox and Logistic regression analysis confirmed that high PANDAR expression was an independent unfavorable risk factor for OS and CR in both observed patient groups.2.The expression of PANDAR in CML was significantly up-regulated,and the difference was statistically significant（P=0.0026）.The results of ROC curve showed that PANDAR might be a potential biomarker for distinguishing CML from normal people（P=0.001）.3.The result showed that expression level of PANDAR in SiRNA-interfered cell lines was significantly lower than that control group（Si-NC）（P=0.0294）.Further experiments showed after 72 hours that the proliferation rate of silenced THP-1 cells was significantly slower than that of the control group（P=0.0026）.CDKN1A was positively correlated with PANDAR in AML,and the overexpression of CDKN1A in AML was correlated with poor prognosis of leukemia.Conclusions:Above results revealed that PANDAR was over-expressed in AML and CML,and that higher PANDAR expression was associated with poor clinical outcome.Our study therefore suggests that PANDAR expression is a promising biomarker for prognostic prediction for AML.In vitro functional experiment,silencing the expression of PANDAR can slow down the proliferation of leukemia cells,which suggested that PANDAR might be related to the development of leukemia.The positive correlation between PANDAR and CDKN1A was verified in clinical specimens,which revealed that PANDAR may be involved in the pathogenesis of leukemia through CDKN1A.