Xue Feng, Li Min, Liu Yun, Xu Chunxin, Li Haigang, Liu Huilian
Department of Clinical Laboratory, Weifang City People's Hospital, No.151 Guangwen Street, Kuiwen District, Weifang, 261041, Shandong, China.
Department of Hematology, Weifang City People's Hospital, Weifang, China.
Biochem Genet. 2023 Feb;61(1):354-371. doi: 10.1007/s10528-022-10244-1. Epub 2022 Aug 2.
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.
急性髓系白血病（AML）是一种常见的造血系统疾病。许多环状RNA（circRNA）在AML中异常表达，包括hsa_circ_0035381（circ_0035381）。然而，circ_0035381在AML中的功能和机制仍大多不清楚。通过qRT-PCR检测circ_0035381的表达。通过进行功能丧失实验验证了circ_0035381对AML细胞增殖、凋亡和线粒体损伤的影响。通过生物信息学分析预测靶向关系，并通过双荧光素酶报告基因和RNA免疫沉淀实验进行验证。circ_0035381在AML骨髓样本和细胞中上调。circ_0035381下调可减少裸鼠体内AML细胞生长，抑制AML细胞增殖，并在体外促进AML细胞凋亡和线粒体损伤。circ_0035381作为miR-582-3p的海绵，miR-582-3p下调可减轻circ_0035381干扰对AML细胞增殖、凋亡和线粒体损伤的影响。miR-582-3p靶向酪氨酸3-单加氧酶/色氨酸5-单加氧酶激活蛋白ζ（YWHAZ），并通过降低YWHAZ表达来抑制AML细胞增殖，促进AML细胞凋亡和线粒体损伤。值得注意的是，circ_0035381通过miR-582-3p调节YWHAZ表达。在AML中，circ_0035381基因敲低通过调节miR-582-3p/YWHAZ轴抑制细胞增殖并促进细胞凋亡和线粒体损伤。
