Hsa_circ_0044907 promotes acute myeloid leukemia progression through upregulating oncogene KIT via sequestering miR-186-5p

ABSTRACT

Background:

It has been reported that circular RNA hsa_circ_0044907 (circ_0044907) expression is overtly elevated in acute myeloid leukemia (AML) patient-derived BMMCs. However, the effect of circ_0044907 on AML progression remains un-clarified.

Methods:

Expression of circ_0044907 in BM and AML cells were detected with real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Cell viability, proliferation, apoptosis, and cycle progression were determined by 3-(4,5-Dimethylthiazol-2-yl)−2,5-Diphenyltetrazolium Bromide (MTT), 5-ethynyl-2’-deoxyuridine (EDU), and flow cytometry assays. The regulatory mechanism of circ_0044907 was predicted by bioinformatics analysis and validated by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. In vivo experiments were carried out to verify the function of circ_0044907.

Results:

Circ_0044907 was overexpressed in AML patient-derived BM and AML cells. Furthermore, circ_0044907 could distinguish AML patients from healthy controls, and high circ_0044907 expression in BM had a poor prognosis for AML patients, implying that circ_0044907 served as a diagnostic and prognostic indicator for AML. Functionally, circ_0044907 silencing reduced cell viability, restrained cell proliferation, arrested cell cycle progression, and induced cell apoptosis in AML cells in vitro. Furthermore, circ_0044907 knockdown decreased AML cell growth in xenograft mouse models. Mechanically, circ_0044907 sponged miR-186-5p to block the inhibiting effect of miR-186-5p on KIT. Silenced miR-186-5p expression weakened circ_0044907 knockdown mediated suppression on AML cell viability, proliferation, and cycle progression. Also, forced KIT expression weakened miR-186-5p upregulation mediated inhibition on AML cell viability, proliferation, and cycle progression.

Conclusion:

Circ_0044907 absorbed miR-186-5p to block the inhibiting impact of miR-186-5p on KIT, thus promoting AML progression.

KEYWORDS:

• AML
• circ_0044907
• miR-186-5p
• KIT

Acknowledgment

None.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Competing interests

The authors declare that they have no competing interest.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request

Authors’ contributions

Ling Liu designed the study, analyzed the data and wrote the manuscript. Xing Qiang performed the experiments and analyzed the data.

Ethics Approval

The research related to human use has been complied with all the relevant national regulations, institutional policies and has been approved by the Ethics Committee of Liangjiang New Area First People's Hospital.