Characterization of hsa_circ_0004277 as a New Biomarker for Acute Myeloid Leukemia via Circular RNA Profile and Bioinformatics Analysis

Abstract

Circular RNAs (circRNAs) represent a widespread class of non-coding RNAs, which drew little attention in the past. Recently, limited data showed their promising future to act as biomarkers in human cancer, but the characteristics and functions remain largely unknown in hematopoietic malignancies, especially in leukemia. In this study, with the help of circRNA microarray, we demonstrated the expression profile of circRNAs in acute myeloid leukemia (AML) patients, and identified a large number of circRNAs possibly expressed in a leukemia specific manner. We also described a circRNA signature related to AML risk-status based on the bioinformatics prediction. In particular, a downregulated circRNA, hsa_circ_0004277, was characterized and functionally evaluated in a cohort of 115 human samples, thus offering a potential diagnostic marker and treatment target in AML. Interestingly, we found chemotherapy could significantly restore the expression of hsa_circ_0004277, indicating the increasing level of hsa_circ_0004277 was associated with successful treatment. Furthermore, a detailed circRNA-miRNA-mRNA interaction network was presented for hsa_circ_0004277, allowing us to better understand its underlying mechanisms for function in AML.

Circ‐U2AF1 promotes human glioma via derepressing neuro‐oncological ventral antigen 2 by sponging hsa‐miR‐7‐5p

“…In this study, we demonstrated that circ-U2AF1 expression was upregulated in glioma tissues, relatively, to adjacent nontumorous tissues. The expression of hsa-mir-7-5p was downregulated, whereas Li et al, 2017;Lu et al, 2017;Meng et al, 2017). Here, we established that circ-U2AF1 might play an oncogene role in glioma.…”

Comprehensive profiling of circular RNA expressions reveals potential diagnostic and prognostic biomarkers in multiple myeloma

“…With the rapid progression and wide application of high-throughput sequencing and microarray, the expression pattern of circRNAs in various human diseases are increasingly reported, and the dysregulated expressions of circRNAs are shown to contribute to the pathogenesis of various cancers [7,[9][10][11][14][15][16][17][18][19]. For instance, in hepatitis B-related HCC, 189 upregulated circRNAs and 37 downregulated circRNAs were found by circRNA microarray, and circRNA_100,338 is further validated to be associated with metastatic progression by acting as an endogenous sponge for miR-141-3p [7].…”

“…With the development of circRNA microarrays, our knowledge about circRNA expression patterns has been initially uncovered in various diseases. In cancer research, circRNA expression patterns have been studied in some solid tumors including breast cancer, esophageal squamous cell cancer, epithelial ovarian cancer, etc., and a number of circRNAs are disclosed to involve in the pathophysiological progression of these malignancies [8][9][10][11]. As for hematological malignancies, an extensive analysis of circRNA expression profiles reveals a total of 464 dysregulated circRNAs (147 upregulated and 317 downregulated) in acute myeloid leukemia (AML) patients compared with healthy controls, and among these circRNAs, circ_0004277 is validated to be positively associated with prognosis in AML patients [9].…”

Expression Profiling Identifies Circular RNA Signature in Hepatoblastoma

“…Differentially expressed circRNAs with statistical significance were identified through fold change filtering or volcano plot filtering. Hierarchical clustering was performed to show the distinguishable circRNA expression pattern among different samples [10, 11]. Circular RNAs exhibiting fold change>2 and P -value<0.05 were selected as significantly differentially expressed circRNAs.…”