Circular RNA BMI1 Serves as a Potential Target for Diagnosis and Treatment in Esophageal Cancer.

AIMS: Previous studies have confirmed that BMI1 is elevated in esophageal cancer, which is a potential therapeutic target for esophageal cancer. However, the clinical significance of circular RNA BMI1 (circ-BMI1) in esophageal cancer is not yet clear. Herein, we revealed the clinical implication of circ-BMI1 in esophageal cancer, and provided a theoretical basis for molecular diagnosis and potential targeted therapy of esophageal cancer. METHODS: Firstly, 10 fresh paired esophageal cancer tissues and paracancer tissues, 49 esophageal cancer serum samples and 28 healthy control serum samples were involved in our study. Differential expression and clinical significance of circ-BMI1 in esophageal cancer patients and healthy controls were evaluated by quantitative Real-time RT-PCR (RT-qPCR). Secondly, effects of circ-BMI1 differential expression on biological function of esophageal cancer cell line Eca109 were analyzed. Effects of circ-BMI1 on cell proliferation, migration and colony forming ability were evaluated by CCK-8, wound healing, and colony-forming assay. Cell apoptosis, drug sensitivity tests were also be conducted. Finally, influence of Eca109 cells differentially expressed by circ-BMI1 on tumorigenicity in nude mice was studied. RESULTS: Expression of circ-BMI1 in serum and tissues of esophageal cancer patients was significantly decreased compared to controls (P < 0.001 and P = 0.003, respectively). Area under the receiver operating characteristic curve (ROC) was 0.726. Cell proliferation, migration and colony forming ability of circBMI1-Eca109 cells were obviously decreased than that of NC-Eca109 cells (P < 0.05). circBMI1-Eca109 cells were more sensitive to 5-fluorouracil and cisplatin, and tumor volume of nude mice in circBMI1-Eca109 group was smaller (P < 0.05). CONCLUSIONS: The study indicated that expression of circ-BMI1 was significantly down-regulated in esophageal cancer. Overexpression of circ-BMI1 inhibited proliferation, migration, colony formation of Eca109 cells, and tumor growth of Eca109 cells in nude mice. circ-BMI1 may be a potential target for diagnosis and treatment in esophageal cancer.

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

PURPOSE: Our research aimed to investigate the expression level of circ_0002232, which is transcribed from PTEN, and find out the association of circ_0002232/miR-92a-3p/PTEN network in acute myeloid leukemia (AML). METHODS: Circ_0002232 expression in 115 AML patients and 48 controls was detected by using real-time quantitative PCR. The diagnostic value of circ_0002232 expression was evaluated by receiver operating characteristic curve. Kaplan-Meier curves were used to analyse the impact of circ_0002232 for overall survival. Associated network of circ_0002232 was predicted by using interaction prediction websites. RESULTS: Compared with controls, circ_0002232 was notably low-expressed in AML (P<0.001). According to the result of receiver operating characteristic curve, circ_0002232 expression could distinguish AML patients from controls (P<0.001). There were significant differences in patients' age (P=0.004), FAB classifications (P=0.036), white blood cell count (P=0.041) and platelet count (P=0.021) between low-expressed circ_0002232 group and high-expressed circ_0002232 group. Moreover, there was a positive correlation between circ_0002232 expression and patients' age (Pearson r=0.256, P=0.0057). Interestingly, we found that patients in low-expressed circ_0002232 group had better overall survival both in whole AML (P=0.030) and non-APL AML (P=0.014). Remarkably, the expression of circ_0002232 was positively correlated with PTEN (Spearman r=0.678, P<0.001). Furthermore, there was a negative correlation in AML between circ_0002232 and miR-92a-3p (Spearman r=-0.301, P=0.016), miR-92a-3p and PTEN (Spearman r=-0.324, P=0.034). Interaction prediction websites revealed that circ_0002232 might affect the expression of PTEN and the process of AML through sponging miR-92a-3p. CONCLUSION: Circ_0002232, one of the circRNAs transcribed from PTEN, 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 association network of circ_0002232/miR-92a-3p/PTEN in AML.

A three-gene signature might predict prognosis in patients with acute myeloid leukemia.

The identification of effective signatures is crucial to predict the prognosis of acute myeloid leukemia (AML). The investigation aimed to identify a new signature for AML prognostic prediction by using the three-gene expression (octamer-binding transcription factor 4 (OCT4), POU domain type 5 transcription factor 1B (POU5F1B) and B-cell-specific Moloney murine leukemia virus integration site-1 pseudogene 1 (BMI1P1). The expressions of genes were obtained from our previous study. Only the specimens in which three genes were all expressed were included in this research. A three-gene signature was constructed by the multivariate Cox regression analyses to divide patients into high-risk and low-risk groups. Receiver operating characteristic (ROC) analysis of the three-gene signature (area under ROC curve (AUC) = 0.901, 95% CI: 0.821-0.981, P<0.001) indicated that it was a more valuable signature for distinguishing between patients and controls than any of the three genes. Moreover, white blood cells (WBCs, P=0.004), platelets (PLTs, P=0.017), percentage of blasts in bone marrow (BM) (P=0.011) and complete remission (CR, P=0.027) had significant differences between two groups. Furthermore, high-risk group had shorter leukemia-free survival (LFS) and overall survival (OS) than low-risk group (P=0.026; P=0.006), and the three-gene signature was a prognostic factor. Our three-gene signature for prognosis prediction in AML may serve as a prognostic biomarker.