Circular RNA ATAD1 is upregulated in acute myeloid leukemia and promotes cancer cell proliferation by downregulating miR‑34b via promoter methylation

Abstract

A previous study has reported the oncogenic role of circular RNA (circ)-ATAD1 in gastric cancer. The aim of the present study was to investigate the role of circ-ATAD1 in acute myeloid leukemia (AML). Bone marrow mononuclear cells were collected from 60 patients with AML and 60 healthy controls, followed by RNA isolation and reverse transcription-quantitative PCR to assess the expression of circ-ATAD1 and microRNA (miR)-34b. A subcellular fractionation assay was used to determine the subcellular location of circ-ATAD1 in AML cells. Furthermore, circ-ATAD1 and miR-34b were overexpressed in AML cells to study crosstalk between the two molecules. The effect of circ-ATAD1 overexpression on miR-34b gene methylation was also analyzed by methylation-specific PCR, and the roles of circ-ATAD1 and miR-34b in the regulation of AML cell proliferation were analyzed by BrdU assay. circ-ATAD1 expression was found to be elevated, and inversely correlated with that of miR-34b, in patients with AML. Subcellular fractionation assays showed that circ-ATAD1 was specifically expressed in the nucleus. In addition, circ-ATAD1 overexpression in AML cells decreased miR-34b expression and increased miR-34b gene methylation. Moreover, AML cell proliferation was increased by circ-ATAD1 overexpression, but decreased by miR-34b overexpression, and the effect of circ-ATAD1 overexpression on AML cell proliferation was reduced by miR-34b overexpression. Together, these results indicate circ-ATAD1 as a nucleus-specific circRNA in AML, which promotes AML cell proliferation by downregulating miR-34b via methylation.

Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination Behavior

“…Our previous studies confirmed that Thorase plays a vital role in removing misplaced α-synuclein from the outer membrane of mitochondria and plays a protective role in neurodegeneration mediated by α-synuclein [ 33 ]. Recently, several research groups have found that circRNA circ-ATAD1 (Thorase) plays a vital role in both solid tumors (such as gastric cancer, colorectal cancer and endometrial cancer) [ 46 , 47 , 48 ] and blood tumors (such as acute myeloid leukemia) [ 49 ]. Multi-omics results showed that downregulation of ATAD1 was a clinical biomarker for the pathological diagnosis and prognosis of prostate adenocarcinoma patients [ 50 ].…”

CircRNA: a rising star in leukemia

“…Acute myelogenous leukemia (AML) is a highly aggressive malignancy of hematopoietic stem cells. A series of studies have shown that circRNAs are aberrantly expressed in AML ( Chang et al, 2022 ; Wu et al, 2021 ). Sun et al (2019) demonstrated that there was a trend of elevated expression of circMYBL2 in AML patients with an FLT3-ITD mutation.…”

MicroRNA-34 Family in Cancers: Role, Mechanism, and Therapeutic Potential

“…Leukemia, particularly acute myelogenous leukemia (AML), is a widespread and challenging form of acute leukemia that accounts for approximately 80% of all cases worldwide [125]. In chronic lymphocytic leukemia (CLL), a regulatory circuit has been discovered.…”