INHBA在急性髓系白血病中的表达及功能预测

斯婷　　陆滢　　唐善浩　　裴仁治

[摘要] 目的 分析抑制素β-A（INHBA）在急性髓系白血病（AML）中的表达，并应用生物信息学技术探索及预测INHBA在AML中的生物学功能。 方法 收集2015年1月至2018年12月我院连续收治的AML患者骨髓标本120例及来源于造血干细胞移植供者的健康成人骨髓标本15例，采用细胞免疫组化、Western Blot、qRT-PCR等方法检测INHBA在AML不同细胞系及AML患者与正常成人中的表达水平;利用STRING数据库及KEGG富集分析构建INHBA蛋白质相互作用网络并预测其功能。 结果 INHBA在AML细胞系（Kasumi-1、KG-1及THP-1）中均有表达;qRT-PCR验证了INHBA在AML中的表达水平均值高于正常对照（0.718 vs 0.377），差异无统计学意义（P=0.286）;蛋白质网络互作分析显示，与INHBA互作得分在0.90 以上的17个蛋白，从高到低分别为FSTL3、ACVR2A、ACVR2B、ACVR1B、ACVR1C、ACVR1、ACVRL1、INHA、ENG、SMAD2、SMAD3、INHBB、SMAD4、IGSF1、FSHB、CGA、FKBP1A;KEGG富集分析显示，INHBA及其互作蛋白主要功能富集于TGF-β信号通路与BMP/Smad信号通路。结论 INHBA在AML中高表达，可能通过调控TGF-β与BMP/Smad信号通路参与肿瘤的发生发展。

[关键词] INHBA;急性髓系白血病;功能预测;生物信息

[中图分类号] R551          [文献标識码] A          [文章编号] 1673-9701（2021）09-0044-04

Expression and function prediction of INHBA in acute myeloid leukemia

SI Ting   LU Ying   TANG Shanhao   PEI Renzhi

Department of Hematology， the Affiliated People's Hospital of Ningbo University， Ningbo   315040， China

[Abstract] Objective To analyze the expression of inhibin β-A （INHBA） in acute myeloid leukemia（AML）， and to explore and predict the biological function of INHBA in AML by applying bioinformatics technology. Methods A total of 120 bone marrow specimens from AML patients in our hospital from January 2015 to December 2018，and 15 healthy adult bone marrow specimens from hematopoietic stem cell transplantation donors were selected. The expression level of INHBA in different AML cell lines， AML patients， and normal adults were detected by cellular immunohistochemistry，Western Blot，and qRT-PCR. STRING database and KEGG enrichment analysis were used to construct INHBA protein interaction network and predict its function. Results INHBA was expressed in AML cell lines（Kasumi-1， KG-1， and THP-1）. The expression level of INHBA in AML was higher than that of the normal control verified by qRT-PCR （0.718 vs 0.377）. The difference between the two groups was no statistically significant（P=0.286）. Protein network interaction analysis showed that 17 proteins with an interaction score above 0.90 with INHBA， from high to low， were FSTL3， ACVR2A， ACVR2B， ACVR1B， ACVR1C， ACVR1， ACVRL1， INHA， ENG， SMAD2， SMAD3， INHBB， SMAD4， IGSF1， FSHB， CGA， FKBP1A. KEGG enrichment analysis showed that the main functions of INHBA and its interacting proteins were enriched in the TGF-β signaling pathway and BMP/Smad signaling pathway. Conclusion INHBA is highly expressed in AML， which may be involved in the occurrence and development of tumors by regulating TGF-β and BMP/Smad signaling pathways.

[Key words] INHBA; Acute myeloid leukemia; Function prediction; Biological information

抑制素β-A（Inhibinβ-A，INHBA）是转化生长因子β（Transforming growth factor β， TGF-β）超家族的一个配体[1]，多项研究发现，INHBA在肺腺癌、食管鳞状细胞癌、胃癌、结肠癌、膀胱上皮癌等肿瘤组织中高表达，且其高表达与患者预后不良相关[2-6]，提示INHBA在肿瘤的发生发展及演进中具有重要意义。本研究团队在前期研究检测了初发急性髓系白血病（Acute myeloid leukemia，AML）患者骨髓单个核细胞（Mononuclear cells，MNCs）中INHBA基因的表达水平，结果显示首次发现INHBA高表达的患者治疗反应差、总体生存率低，INHBA高表达是AML患者预后不良的独立危险因素[7]。但目前INHBA在AML中的作用机制尚未揭示，其可能生物学功能尚未明确。……