Hsa_circ_0012152 and Hsa_circ_0001857 Accurately Discriminate Acute Lymphoblastic Leukemia From Acute Myeloid Leukemia

Abstract

Acute leukemia (AL) is a group of highly heterogeneous hematological malignancies. Circular RNAs (circRNAs) are covalently closed circRNA molecules implicated in the development of many diseases. However, the role of circRNAs in AL remains largely unknown. Therefore, this study aimed to identify new classification diagnostic biomarkers for subgroups of AL. The circRNA expression signatures discriminating acute lymphoblastic leukemia (ALL) from acute myeloid leukemia (AML) were identified by microarray, followed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) validation. Receiver operating characteristic curve analysis was used to evaluate the diagnostic efficiencies of hsa_circ_0001857 and hsa_circ_0012152, and hsa_circ_0012152 was selected for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The results showed that the circRNA expression profiles, hsa_circ_0001857, and hsa_circ_0012152 could clearly discriminate ALL from AML. The target genes of hsa_circ_0012152 might be involved in biological processes, such as myeloid cell differentiation, covalent chromatin modification, histone modification, and rat sarcoma (Ras) protein signal transduction, and participate in pathways such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3′-kinase (PI3K)-Akt signaling pathway. Hsa_circ_0012152 might be involved in the initiation and development of AML through miR-491-5p/epidermal growth factor receptor (EGFR)/MAPK1 or miR-512-3p/EGFR/MAPK1 axis. Our results showed that circRNA expression profiles and specifically expressed circRNAs were promising classification biomarkers to designate AL into ALL or AML.

Circ_0009910 sponges miR‐491‐5p to promote acute myeloid leukemia progression through modulating B4GALT5 expression and PI3K/AKT signaling pathway

“…35 Similarly, miR-491-5p was certified to participate in leukemia progression and it was low expressed in ALL cells. 18,36 Similar to this result, miR-491-5p was downregulated in AML tissues and cells in this study. In addition, miR-491-5p expression was negatively related to circ_0009910 level in AML tissues, and miR-491-5p silence could overturn circ_0009910 knockdown-mediated effects on AML cell progression.…”

Downregulation of circ_0012152 inhibits proliferation and induces apoptosis in acute myeloid leukemia cells through the miR‐625‐5p/SOX12 axis

“…9,10 For instance, circRAD18 facilitated AML progression through modulating miR-206/PRKACB pathway. 27 Moreover, circ_0012152, derived from RNF220, was demonstrated to be highly expressed in AML tissues relative to normal tissues, 12 but its special molecular mechanism in AML remains largely elusive. Consistent with above research, in this study, circ_0012152 was found to be upregulated in AML, and high circ_0012152 expression was closely related to overall survival.…”

MLL-SEPT5 Fusion Transcript in Myelodysplastic Syndrome Patient With t(11;22)(q23;q11)

“…Sequences of the primers are as follows: MLL-E7, 5 ′ -TACAGGACCGCCAAGAA-3 ′ from exon 7 of MLL; SEPT5-E3, 5 ′ -CAAAGCCTTTCTTCACCGAC-3 ′ from exon 3 of SEPT5; SEPT5-E5, 5 ′ -TGTCCACGATGGTGAGCTTC-3 ′ from exon 5 of SEPT5. About 1 µl cDNA was used for amplification in a total volume of 20 with 0.8 µl of forward primer, 0.8 µl of reverse primer, 10 µl of SYBR Green (Takara, Japan), 0.4 µl of ROX, and 7 µl of RNase-free H 2 O. PCR procedures were carried out as described previously (9). The products were analyzed by electrophoresis with a 1% agarose gel and were then sequenced by the Shanghai Sangong Biotech Corporation (Shanghai, China).…”