基于生物信息学的方法鉴定 SPNS3（Spinster 同源物 3）为急性髓系白血病细胞凋亡抵抗的预后生物标志物。

Bioinformatics-based identification of SPNS3 (Spinster homolog 3) as a prognostic biomarker of apoptosis resistance in acute myeloid leukemia.

机构信息

Department of Hematology, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Suzhou, China.

Institute of Blood and Marrow Transplantation, Medical College of Soochow University, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, National Clinical Research Center for Hematologic Diseases, Soochow University, Suzhou, China.

出版信息

Bioengineered. 2021 Dec;12(1):7837-7848. doi: 10.1080/21655979.2021.1982303.

DOI:10.1080/21655979.2021.1982303

PMID:34608834

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8806827/

Abstract

Spinster homolog 3 (SPNS3) belongs to the Spinster (SPNS) family which participates in sphingolipid transportation through the cell membrane. However, the functions of SPNS3 in acute myeloid leukemia (AML) are unknown. This study obtained SPNS3 from a gene set that was related to AML relapse and evaluate whether high SPNS3 expression induced apoptosis resistance in an AML cell line, which is consistent with the role of SPNS3 as a marker of poor prognosis in the clinic. Moreover, internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3-ITD) mutation and the AC127521.1/ MIR-139/SPNS3 competing endogenous RNA axis were found to regulate SPNS3 expression. In addition, we noted that SPNS3 may play an important role in the Sphingosine-1-phosphate signal pathway that is involved in the maintenance of the AML microenvironment. These results highlight the anti-apoptosis effect of SPNS3 in AML, and the potential mechanism mediating this effect was explored through bioinformatics. AML: acute myeloid leukemia; FLT3-ITD: internal tandem duplication of FMS-like tyrosine kinase 3; SPNS3: spinster homolog 3; SPNS1: spinster homolog 1; SPNS2: spinster homolog 2; GO: gene ontology; S1P: sphingosine-1-phosphate; ceRNA: competing endogenous RNA; dAML: acute myeloid leukemia at diagnosis; iAML: acute myeloid leukemia after induction chemotherapy; rAML: acute myeloid leukemia at relapse; DEGs: differentially expressed genes; BP: biological processes; CC: cellular components; MF: molecular functions; MRD: minimal residual disease; EFS: event-free survival; OS: overall survival; KEGG: Kyoto Encyclopedia of Genes and Genomes; SPHK: Sphingosine kinase.

摘要

螺旋体同源物 3（SPNS3）属于螺旋体（SPNS）家族，该家族通过细胞膜参与神经酰胺运输。然而，SPNS3 在急性髓系白血病（AML）中的作用尚不清楚。本研究从与 AML 复发相关的基因集中获得 SPNS3，并评估高 SPNS3 表达是否诱导 AML 细胞系中的凋亡抵抗，这与 SPNS3 作为临床预后不良标志物的作用一致。此外，还发现 FMS 样酪氨酸激酶 3（FLT3-ITD）突变的内部串联重复和 AC127521.1/MIR-139/SPNS3 竞争性内源性 RNA 轴调节 SPNS3 的表达。此外，我们注意到 SPNS3 可能在鞘氨醇-1-磷酸信号通路中发挥重要作用，该通路参与 AML 微环境的维持。这些结果强调了 SPNS3 在 AML 中的抗凋亡作用，并通过生物信息学探讨了介导这种作用的潜在机制。AML：急性髓系白血病；FLT3-ITD：FMS 样酪氨酸激酶 3 的内部串联重复；SPNS3：螺旋体同源物 3；SPNS1：螺旋体同源物 1；SPNS2：螺旋体同源物 2；GO：基因本体论；S1P：鞘氨醇-1-磷酸；ceRNA：竞争性内源性 RNA；dAML：诊断时的急性髓系白血病；iAML：诱导化疗后的急性髓系白血病；rAML：复发时的急性髓系白血病；DEGs：差异表达基因；BP：生物过程；CC：细胞成分；MF：分子功能；MRD：微小残留病；EFS：无事件生存；OS：总生存；KEGG：京都基因与基因组百科全书；SPHK：鞘氨醇激酶。