Circ_0100160 Derived from FLT3 Is a Novel Diagnostic Biomarker in Acute Myeloid Leukemia

Abstract

Background: Acute myeloid leukemia (AML) is a genetically diverse and aggressive hematological malignancy. A growing number of studies suggest circRNAs are potential prognostic and diagnostic biomarkers in cancer. In previous high-throughput sequencing of circRNAs, we found up-regulated circ_0100160 in AML. Methods: As a follow-up to circRNA-seq analysis, qRT-PCR was used in this study to further validate the expression levels of circ_0100160 in AML cells from primary patients. The expression of circ_0100160 in AML cells was knockdown by lentiviral infection, and cell proliferation, apoptosis, and cell cycle were performed. AML mice models with low circ-0100160 were constructed to observe the mice survival and organ leukemiacellinfiltration. Comprehensive identification of RNA binding proteins by mass spectrometry (ChIRP-MS) were performed to reveal the composition and dynamics of specific noncoding RNA-protein complexes (RNPs) . Results: The circ_0100160 is significantly highly expressed in AML patients, and its expression level can be well used to identify AML. In vitro, knockdown of circ_0100160 could significantly inhibit the proliferation of AML cells, while promoting cell apoptosis. In vivo, AML mice had prolonged survival and slower weight loss after knockdown of circ_0100160, and showed no infiltration of kidney tissue compared with controls. ChIRP-MS found a total of 159 proteins interacing with circ_0100160 and some of them may become RNPs with circ_0100160, and the KEGG pathway analysis suggested the biological functions of the enriched proteins are spliceosome, carbon metabolism and citrate cycle et.al. Conclusion: Circ_0100160 was highly expressed and could enhance the proliferation in AML, which might be a potential therapeutic target for AML treatment.