Circ-ANAPC7 is Upregulated in Acute Myeloid Leukemia and Appears to Target the MiR-181 Family

Abstract

Background/Aims: Circular RNAs (circRNAs) are a family of novel non-coding RNAs associated with various diseases, especially cancer. Recent studies have demonstrated that circRNAs participate in pathogenesis mainly by acting as microRNA (miRNA) sponges. The expression profile of circRNAs in acute myeloid leukemia (AML) has rarely been reported. Methods: Profiles of circRNAs were analyzed using an Arraystar human circRNA microarray with 5 bone marrow samples from patients with newly diagnosed AML and 5 from patients with iron-deficiency anemia. Quantitative reverse transcription PCR was used to validate the expression pattern of circRNAs. Furthermore, circRNA–miRNA network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied. Results: CircRNA microarray analysis revealed that 698 circRNAs were differentially expressed in AML patients, with 282 circRNAs found to be upregulated and 416 to be downregulated. Quantitative reverse transcription PCR showed that circ-ANAPC7 was significantly upregulated in AML. Bioinformatics analysis predicted that circ-ANAPC7 acts as a sponge for the miR-181 family, KEGG analysis revealed that it is associated with cancer-related pathways, and GO analysis indicated that most of its target genes are involved in biological processes. Conclusions: These findings show that circ-ANAPC7 is a promising biomarker for AML, and that it might participate in AML pathogenesis by acting as a sponge for the miR-181 family.

Role of microRNAs, circRNAs and long noncoding RNAs in acute myeloid leukemia

“…A circRNA HIPK2, for example, sponged miR-124-3p to regulate the differentiation of all-trans retinoic acid (ATRA)-induced NB4 cells [155]. Chen et al [151] reported that circANAPC7 was significantly upregulated in AML and used an Arraystar human circRNAs microarray and bioinformatics analysis to predict when ANAPC7 might bind miR-181 family to participate in AML pathogenesis. An oncogenic activity of circRNA was also shown by DLEU2, which was highly expressed in AML, that inhibited miR-496 expression to promote cell proliferation and inhibit cell apoptosis [157].…”

Overexpressed circ_0067934 acts as an oncogene to facilitate cervical cancer progression via the miR‐545/EIF3C axis

“…For example, circRNA8924 is reported to promote proliferation and metastasis of CC cells through regulating CBX8 expression (J. Liu, Wang, Long, Liu, & Li, ). Also, circ‐ANAPC7 upregulation in acute myeloid leukemia promotes tumor progression through the miR‐181 family (H. Chen et al, ). In addition, circRNA circ‐BANP facilitates lung cancer development by the miR‐503/LARP1 pathway (Han et al, ).…”

<p>Biological Roles and Mechanisms of Circular RNA in Human Cancers</p>

“…228 Similarly, the following circRNAs also function as a miRNA sponge in acute myeloid leukemia, such as circ_0009910 sponging miR-20a-5p, circ_100290 sponging to miR-203 and circ-ANAPC7 sponging to miR-181. [229][230][231] Furthermore, recent studies observed that circ-Foxo3 could compete with Foxo3 for binding to some miRNAs and then regulated the expression of Foxo3. 232 Circ-Foxo3 and Foxo3 were frequently decreased in AML and positively associated with each other.…”