Cui He, Lan Xi, Lu Shemin, Zhang Fujun, Zhang Wanggang
Department of Clinical Hematology, Affiliated No. 2 Hospital, Xi'an Jiaotong University, The West Five Road, 157#, Xi'an, Shaanxi 710004, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, The Yanta West Road, 76#, Xi'an, Shaanxi 710061, China.
J Pharm Anal. 2017 Feb;7(1):10-18. doi: 10.1016/j.jpha.2016.09.003. Epub 2016 Nov 2.
Our previous study demonstrated that human KIAA0100 gene was a novel acute monocytic leukemia-associated antigen (MLAA) gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. Here, firstly, bioinformatic prediction of human KIAA0100 gene was carried out using online softwares; Secondly, Human KIAA0100 gene expression was downregulated by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system in U937 cells. Cell proliferation and apoptosis were next evaluated in KIAA0100-knockdown U937 cells. The bioinformatic prediction showed that human KIAA0100 gene was located on 17q11.2, and human KIAA0100 protein was located in the secretory pathway. Besides, human KIAA0100 protein contained a signalpeptide, a transmembrane region, three types of secondary structures (alpha helix, extended strand, and random coil) , and four domains from mitochondrial protein 27 (FMP27). The observation on functional characterization of human KIAA0100 gene revealed that its downregulation inhibited cell proliferation, and promoted cell apoptosis in U937 cells. To summarize, these results suggest human KIAA0100 gene possibly comes within mitochondrial genome; moreover, it is a novel anti-apoptotic factor related to carcinogenesis or progression in acute monocytic leukemia, and may be a potential target for immunotherapy against acute monocytic leukemia.
我们之前的研究表明,人类KIAA0100基因是一种新型的急性单核细胞白血病相关抗原(MLAA)基因。但迄今为止,人类KIAA0100基因的功能特性仍不清楚。在此,首先使用在线软件对人类KIAA0100基因进行生物信息学预测;其次,利用成簇规律间隔短回文重复序列(CRISPR)/CRISPR相关蛋白9(Cas9)系统在U937细胞中下调人类KIAA0100基因的表达。接下来评估KIAA0100基因敲低的U937细胞的细胞增殖和凋亡情况。生物信息学预测显示,人类KIAA0100基因位于17q11.2,人类KIAA0100蛋白位于分泌途径中。此外,人类KIAA0100蛋白包含一个信号肽、一个跨膜区域、三种二级结构(α螺旋、延伸链和无规卷曲)以及来自线粒体蛋白27(FMP27)的四个结构域。对人类KIAA0100基因功能特性的观察表明,其下调抑制了U937细胞的增殖,并促进了细胞凋亡。综上所述,这些结果表明人类KIAA0100基因可能属于线粒体基因组;此外,它是一种与急性单核细胞白血病发生或进展相关的新型抗凋亡因子,可能是急性单核细胞白血病免疫治疗的潜在靶点。