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

Wu,Yarong; Gao,Bingjun; Qi,Xiaolei; Bai,Liyun; Li,Bixin; Bao,Hongjing; Wu,Xi; Wu,Xiaoyun; Zhao,Yuxia

doi:10.3892/ol.2021.13060

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

Authors:
- Yarong Wu
- Bingjun Gao
- Xiaolei Qi
- Liyun Bai
- Bixin Li
- Hongjing Bao
- Xi Wu
- Xiaoyun Wu
- Yuxia Zhao
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Affiliations: Department of Hematology, The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Danyang, Jiangsu 212300, P.R. China, Department of Osteology, The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Danyang, Jiangsu 212300, P.R. China, Department of Hematology, The People's Hospital of Xing'an League, Ulanhot, Inner Mongolia Autonomous Region 137499, P.R. China, Department of Ultrasound, The People's Hospital of Xing'an League, Ulanhot, Inner Mongolia Autonomous Region 137499, P.R. China, Department of Neurosurgery, The People's Hospital of Xing'an League, Ulanhot, Inner Mongolia Autonomous Region 137499, P.R. China, Department of Technology, Research Center for Hua‑Da Precision Medicine of Inner Mongolia Autonomous Region, Hohhot, Inner Mongolia Autonomous Region 010000, P.R. China
Published online on: September 20, 2021 https://doi.org/10.3892/ol.2021.13060
Article Number: 799
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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