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Circ_0035381 Regulates Acute Myeloid Leukemia Development by Modulating YWHAZ Expression via Adsorbing miR-582-3p

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Abstract

Acute myeloid leukemia (AML) is a common hematopoietic disorder. Many circular RNAs (circRNAs) are abnormally expressed in AML, including hsa_circ_0035381 (circ_0035381). Nevertheless, the function and mechanism of circ_0035381 in AML remain mostly unclear. Expression of circ_0035381 was determined by qRT-PCR. The impacts of circ_0035381 on AML cell proliferation, apoptosis, and mitochondrial damage were validated via performing loss-of-function experiments. Targeting relationship was predicted by bioinformatics analysis and verified via dual-luciferase reporter and RNA immunoprecipitation assays. Circ_0035381 was upregulated in AML bone marrow samples and cells. Circ_0035381 downregulation decreased AML cell growth in nude mice and restrained AML cell proliferation and contributed to AML apoptosis and mitochondrial damage in vitro. Circ_0035381 acted as a miR-582-3p sponge, and miR-582-3p downregulation mitigated the impacts of circ_0035381 interference on AML cell proliferation, apoptosis, and mitochondrial damage. MiR-582-3p targeted Tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein zeta (YWHAZ), and it restrained AML cell proliferation and facilitated AML cell apoptosis and mitochondrial damage by decreasing YWHAZ expression. Notably, circ_0035381 regulated YWHAZ expression via miR-582-3p. Circ_0035381 knockdown repressed cell proliferation and promoted cell apoptosis and mitochondrial damage via regulating the miR-582-3p/YWHAZ axis in AML.

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Acknowledgements

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Funding

This work was supported by Scientific Research Project of Weifang City Health Commission (Grant No. Wfwsjk_2019_069).

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  1. Feng Xue and Hui-lian Liu as co-corresponding authors.

Authors and Affiliations

  1. Department of Clinical Laboratory, Weifang City People’s Hospital, No.151 Guangwen Street, Kuiwen District, Weifang, 261041, Shandong, China

    Feng Xue, Min Li, Chunxin Xu & Haigang Li

  2. Department of Hematology, Weifang City People’s Hospital, Weifang, China

    Yun Liu

  3. Biological and Agricultural, Engineering College of Weifang University, No. 5147 Dongfeng East Street, Kuiwen District, Weifang, 261061, Shandong, China

    Huilian Liu

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  1. Feng Xue
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All authors made substantial contribution to conception and design, acquisition of the data, or analysis and interpretation of the data; take part in drafting the article or revising it critically for important intellectual content; gave final approval of the revision to be published; and agree to be accountable for all aspect of the work.

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Xue, F., Li, M., Liu, Y. et al. Circ_0035381 Regulates Acute Myeloid Leukemia Development by Modulating YWHAZ Expression via Adsorbing miR-582-3p. Biochem Genet 61, 354–371 (2023). https://doi.org/10.1007/s10528-022-10244-1

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