Circ_0002232 Acts as a Potential Biomarker for AML and Reveals a Potential ceRNA Network of Circ_0002232/miR-92a-3p/PTEN

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background: </jats:bold><jats:italic>PTEN</jats:italic>, known as a classical tumor suppressor, has been reported to be down-expressed in acute myeloid leukemia (AML) and affected the progression of AML patients. CircRNAs, an emerging type of non-coding RNAs, could act as competing endogenous RNAs (ceRNAs) and has been reported to regulate the expression of <jats:italic>PTEN</jats:italic> through sponging miRNA in many solid tumors. But there are rarely studies focused on the role of <jats:italic>circ-PTEN</jats:italic> in AML. Our research was aimed to investigate the expression level of <jats:italic>circ_0002232</jats:italic>, one of circular RNAs of <jats:italic>PTEN</jats:italic>, reveal the clinical significance and potential ceRNA interaction network in AML of it.<jats:bold>Methods:</jats:bold> <jats:italic>Circ_0002232</jats:italic> expression in 117 AML patients and 48 controls was detected by using Real-time quantitative PCR. The diagnostic value of<jats:italic> circ_0002232</jats:italic> expression was evaluated by receiver operating characteristic curve. Kaplan-Meier curves were used to analyse the impact of <jats:italic>circ_0002232 </jats:italic>for overall survival. CeRNA network of <jats:italic>circ_0002232</jats:italic> was predicted by using interaction prediction websites.<jats:bold>Results:</jats:bold> Compared with controls, <jats:italic>circ_0002232</jats:italic> was notably low-expressed in AML (<jats:italic>P&lt;</jats:italic>0.001). According to the result of receiver operating characteristic curve, <jats:italic>circ_0002232</jats:italic> expression could distinguish AML patients from controls (<jats:italic>P&lt;</jats:italic>0.001). There were significant differences in patients’ age (<jats:italic>P=</jats:italic>0.002), FAB classifications (<jats:italic>P=</jats:italic>0.025), white blood cell count (<jats:italic>P=</jats:italic>0.034) and platelet count (<jats:italic>P=</jats:italic>0.047) between low-expressed <jats:italic>circ_0002232</jats:italic> group and high-expressed <jats:italic>circ_00022332</jats:italic> group. Moreover, there was a positive correlation between <jats:italic>circ_0002232</jats:italic> expression and patients’ age (Pearson r=0.256, <jats:italic>P=</jats:italic>0.0053). Interestingly, we found that patients in low-expressed <jats:italic>circ_0002232</jats:italic> group had better overall survival both in whole AML (<jats:italic>P=</jats:italic>0.019) and non-APL AML (<jats:italic>P=</jats:italic>0.044). Remarkably, the expression of <jats:italic>circ_0002232 </jats:italic>was positively correlated with <jats:italic>PTEN </jats:italic>(Pearson r=0.769, <jats:italic>P&lt;</jats:italic>0.001). Furthermore, there was a negative correlation in AML between <jats:italic>circ_0002232 </jats:italic>and<jats:italic> miR-92a-3p </jats:italic>(Pearson r=-0.262, <jats:italic>P=</jats:italic>0.032), <jats:italic>miR-92a-3p </jats:italic>and<jats:italic> PTEN</jats:italic> (Pearson r=-0.358, <jats:italic>P=</jats:italic>0.019). Interaction prediction websites revealed that <jats:italic>circ_0002232</jats:italic> might regulate the expression of <jats:italic>PTEN </jats:italic>through sponging <jats:italic>miR-92a-3p</jats:italic> and affect the process of AML.<jats:bold>Conclusions:</jats:bold> <jats:italic>Circ_0002232</jats:italic>, one of circRNAs of <jats:italic>PTEN</jats:italic>, was remarkably down-regulated in AML and could act as a promising biomarker for the diagnosis of AML. In addition, there might be a potential ceRNA interaction network of <jats:italic>circ_0002232/miR-92a-3p/PTEN</jats:italic> in AML.</jats:p>