A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia

Abstract

Background As a common haematological malignancy, acute myeloid leukaemia (AML), particularly with extramedullary infiltration (EMI), often results in a high mortality rate and poor prognosis. Circular RNAs (circRNAs) regulate biological and pathogenic processes, suggesting a potential role in AML. We have previously described the overall alterations in circRNAs and their regulatory networks between patients with AML presenting with and without EMI. This study aims to find new prognostic and therapeutic targets potentially associated with AML. Methods qRT-PCR was performed on samples from 40 patients with AML and 15 healthy controls. The possibility of using circPLXNB2 (circRNA derived from PLXNB2) as a diagnostic and prognostic biomarker for AML was analysed with multiple statistical methods. In vitro, the function of circPLXNB2 was studied by lentivirus transfection, CCK-8 assays, flow cytometry, and Transwell experiments. Western blotting and qRT-PCR were performed to detect the expression of related proteins and genes. The distribution of circPLXNB2 in cells was observed using RNA fluorescence in situ hybridization (RNA-FISH). We also investigated the role of circPLXNB2 by establishing AML xenograft models in NOD/SCID mice. Results By analysing the results of qRT-PCR detection of clinical samples, the expression of the circPLXNB2 and PLXNB2 mRNAs were significantly increased in patients with AML, more specifically in patients with AML presenting with EMI. High circPLXNB2 expression was associated with an obviously shorter overall survival and leukaemia-free survival of patients with AML. The circPLXNB2 expression was positively correlated with PLXNB2 mRNA expression, as evidenced by Pearson’s correlation analysis. RNA-FISH revealed that circPLXNB2 is mainly located in the nucleus. In vitro and in vivo, circPLXNB2 promoted cell proliferation and migration and inhibited apoptosis. Notably, circPLXNB2 also increased the expression of PLXNB2, BCL2 and cyclin D1, and reduced the expression of BAX. Conclusion In summary, we validated the high expression of circPLXNB2 and PLXNB2 in patients with AML. Elevated circPLXNB2 levels were associated with poor clinical outcomes in patients with AML. Importantly, circPLXNB2 accelerated tumour growth and progression, possibly by regulating PLXNB2 expression. Our study highlights the potential of circPLXNB2 as a new prognostic predictor and therapeutic target for AML in the future.

Potential Immune Biomarker Candidates and Immune Subtypes of Lung Adenocarcinoma for Developing mRNA Vaccines

“…Therefore, these LUAD-associated immune biomarkers were presented by antigen-presenting cells (macrophages and DCs) to activate T cells for initiating the immune response. Accumulated (46). Next, SLC9A4 is also known as sodium-hydrogen exchanger (NHE) 4 protein.…”

“…Those patients had poor OS and disease-free survival (PFS), which is consistent with our study. They also indicated that PLXNB2 promoted proliferation and migration and that suppressed apoptosis both in vivo and in vitro ( 46 ). Next, SLC9A4 is also known as sodium–hydrogen exchanger (NHE) 4 protein.…”

Functions and clinical significance of circular RNAs in acute myeloid leukemia

“…Lin et al found that enhanced circPLXNB2 levels were related to an obviously shorter overall survival and leukaemia-free survival of patients with AML. Their study highlights the potential of circPLXNB2 as a novel prognostic marker and therapeutic target for AML in the future ( Lin et al, 2021 ) ( Figure 5A ). In other studies, they found that hsa_circ_0075451, circ-VIM and circ_0009910 can serve as important prognostic factor in AML, respectively ( Ping et al, 2019 ; Yi et al, 2019 ; Wang J. H. et al, 2021 ).…”

Predicting the influence of Circ_0059706 expression on prognosis in patients with acute myeloid leukemia using classical statistics and machine learning

“…Hence, circRNAs have high stability, as well as specificity, which contribute to its good potential for application in the field of tumor biomarkers (Xu et al, 2019;Wang et al, 2021;Wei et al, 2020). Some circRNA molecules are abnormally expressed in AML and associated with patient prognosis (Chen et al, 2018;Sun et al, 2019;Lin et al, 2021); for example, circ-VIM is significantly upregulated in AML, and its over-expression is an independent prognostic factor associated with duration of overall and leukemia-free survival of patients with AML (Yi et al, 2019).…”