Long noncoding RNA SATB1-AS1 contributes to the chemotherapy resistance through the microRNA-580/ 2’-5’-oligoadenylate synthetase 2 axis in acute myeloid leukemia

Bioengineered

Xiaofeng Jia¹  Hong Zhou²  Pengfei Shi²  Fan Yang² 

[1] College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang, P.R. Chin;Department of Hematology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. Chin;

关键词: Acute myeloid leukemia;    long noncoding RNA SATB1-AS1;    microRNA-580;    OAS2;    chemotherapy resistance;    GSK3β/β-catenin pathway;   

DOI  :  10.1080/21655979.2021.1971508

来源: Taylor & Francis

【 摘 要 】

Acute myeloid leukemia (AML) represents a hematopoietic cancer with an invasive property. Chemoresistance blunts the therapeutic effect of chemotherapeutics in AML. Long noncoding RNAs (lncRNAs) have been implicated in chemotherapy resistance in AML. Transcriptome sequencing in the current study was applied to clarify the differentially expressed lncRNAs between peripheral blood mononuclear cells of AML and normal samples. The expression of special AT-rich sequence binding protein 1 antisense RNA 1 (SATB1-AS1) and 2ʹ-5ʹ-oligoadenylate synthetase 2 (OAS2) in AML patients was evaluated by qRT-PCR. The relationships among SATB1-AS1, microRNA-580 (miR-580) and OAS2 were investigated by dual-luciferase reporter assay. We observed that SATB1-AS1 and OAS2 were upregulated, while miR-580 was downregulated in AML patients. SATB1-AS1 depletion suppressed proliferation, and enhanced apoptosis and sensitivity of AML cells. Additionally, SATB1-AS1 promoted the expression of OAS2 by acting as a molecular sponge of miR-580 in AML. miR-580 downregulation, OAS2 overexpression and a selective glycogen synthase kinase (GSK)-3β inhibitor AR-A014418 abolished the effects of SATB1-AS1 deletion on the chemosensitivity of AML cells. In conclusion, SATB1-AS1 knockdown promotes the sensitivity of AML cells by upregulating miR-580 and downregulating OAS2 through the GSK3β/β-catenin pathway, providing new insights into the function of SATB1-AS1 as a miRNA sponge in AML.

【 授权许可】

CC BY