Recently, circRNA, a large family of noncoding RNAs (ncRNAs), received extensive attention of researchers along with the development of transcriptome sequencing technologies. CircRNAs are alternative transcripts from exonic backsplicing of coding genes (exonic circRNAs) in mammalian cells, with abundant, stable, evolutionarily conserved and cell-type specific characteristics (18). Some circRNAs called miRNA sponges have miRNA response elements (MREs) and display important miRNA activities, enhancing the complexity of RNA regulatory networks and being involved in gene expression(19, 20).
A growing number of studies highlight the diagnostic and therapeutic potential of circRNAs in many types of cancers. CircRNA_100269 was downregulated in gastric cancer (GC) and suppresses tumor cell growth by targeting miR-630, which comprised a novel pathway that regulates proliferation of GC cells (21). CircRNA_100782 regulated the proliferation of pancreatic carcinoma by acting as miR-124 sponge through the IL6-STAT3 pathway (22). In non-small cell lung cancer, hsa_circ_0007385 knockdown resulted in significant suppression of the proliferation, migration and invasion of NSCLC cells(23). Microarray profiling and bioinformatics analyses were also performed in esophageal cancer (24) and cardiac fibroblasts(25).
Furthermore, the expression profile of circRNAs in AML patients has been done in one study, and a large number of circRNAs possibly expressed in a leukemia specific manner are identified, especially hsa_circ_0004277, which was down-expressed in AML patients compared with healthy controls (17). Another study showed that hsa_circ_0075001 expression correlates positively with total NPM1 expression in AML, but is independent of the NPM1 mutational status (16).
In our previous investigation, we also demonstrated a different circRNAs expression profiling in AML patients, and one circRNA named circ-ANAPC7 was significantly upregulated in AML patients in our preliminary validation(26). As for this study, we enlarge the number of clinical samples to verify the result before and illuminate the relationship between expression level of circ-ANAPC7 and the clinical features of AML patients. The results showed circ-ANAPC7 was significantly upregulated in AML patients, which was in line with the result before. Furthermore, we found that the expression level of circ-ANAPC7 was related to the count of WBC, but not the FAB type, risk statue, percentage of blasts in bone marrow, indicating that the altered expression level of circ-ANAPC7 may be related to the pathogenesis of AML, but not the types or risk statues of AML. Survival analysis predicted the expression level of circ-ANAPC7 had no influence on the OS and DFS, that is, it could not be used as a prognostic factor in AML.
The count of WBC, blast percentage in the bone marrow and refractory AML was the independent factors for survival of AML patients, which were consistent with the previous study(27, 28). ROC analysis stated that circ-ANAPC7 have greatly potential diagnostic value for AML. Ambulatory monitoring of expression of circ-ANAPC7 in matched-pair AML samples showed it changed accompanied with the disease condition transformation. Therefore, we speculate that the expression level of circ-ANAPC7 might be used as a predictive index for supervising early recurrence, advising inchoate treatment to prolong OS.
According to bioinformatics analysis in our previous research, we have predicted that circ-ANAPC7 may function as a sponge to adsorb miR-181 family(26). MiR-181 has been proved upregulated in AML, which was related to longer OS of AML patients(29, 30). Furthermore, elevated miR-181 expression was associated with increased survival in 395 American patients, and reduced survival in 325 Chinese one, which indicated that miR-181 can be used as a promising prognostic biomarker in AML patients, depending on the origin of patient population.(31) In a subsequent study, we will devote ourselves to dig out the mechanism between circ-ANAPC7 and miR-181.
However, there is still some limitation in our study. First, the sample size of our study is still relatively small, and these data should be confirmed in large-scale studies and populations with different races and regions. Second, we do not have data in circ-ANAPC7 expression level of plasma or serum from AML patients, which is our next research plan.