Zhang Rengjing, Zhao Chen, Xiong Zixiang, Zhou Xiaobo
Electrical and Computer Engineering Department, Texas A&M University, College Station, TX 77840, USA.
Radiology Comprehensive Cancer Center Cancer Biology, Wake Forest University, Winston-Salem, NC 27103, USA.
Biomed Res Int. 2014;2014:351095. doi: 10.1155/2014/351095. Epub 2014 Apr 16.
Ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) is a protein with unknown function. Frequently methylated or downregulated, OCIAD2 has been observed in kinds of tumors, and TGFβ signaling has been proved to induce the expression of OCIAD2. However, current pathway analysis tools do not cover the genes without reported interactions like OCIAD2 and also miss some significant genes with relatively lower expression. To investigate potential biological milieu of OCIAD2, especially in cancer microenvironment, a nova approach pbMOO was created to find the potential pathways from TGFβ to OCIAD2 by searching on the pathway bridge, which consisted of cancer enriched looping patterns from the complicated entire protein interactions network. The pbMOO approach was further applied to study the modulator of ligand TGFβ1, receptor TGFβR1, intermediate transfer proteins, transcription factor, and signature OCIAD2. Verified by literature and public database, the pathway TGFβ1-TGFβR1-SMAD2/3-SMAD4/AR-OCIAD2 was detected, which concealed the androgen receptor (AR) which was the possible transcription factor of OCIAD2 in TGFβsignal, and it well explained the mechanism of TGFβ induced OCIAD2 expression in cancer microenvironment, therefore providing an important clue for the future functional analysis of OCIAD2 in tumor pathogenesis.
卵巢癌免疫反应抗原样蛋白2（OCIAD2）是一种功能未知的蛋白质。OCIAD2经常发生甲基化或表达下调，在多种肿瘤中均有发现，并且已证实转化生长因子β（TGFβ）信号可诱导OCIAD2的表达。然而，当前的通路分析工具并未涵盖像OCIAD2这样没有报道过相互作用的基因，同时也遗漏了一些表达相对较低的重要基因。为了研究OCIAD2潜在的生物学环境，尤其是在癌症微环境中的情况，创建了一种新方法pbMOO，通过在通路桥梁上进行搜索来寻找从TGFβ到OCIAD2的潜在通路，该通路桥梁由复杂的整个蛋白质相互作用网络中富含癌症的环状模式组成。pbMOO方法进一步应用于研究配体TGFβ1、受体TGFβR1、中间转运蛋白、转录因子和标志性蛋白OCIAD2的调节因子。经文献和公共数据库验证，检测到了TGFβ1 - TGFβR1 - SMAD2/3 - SMAD4/AR - OCIAD2通路，该通路隐藏了雄激素受体（AR），其可能是TGFβ信号中OCIAD2的转录因子，很好地解释了TGFβ在癌症微环境中诱导OCIAD2表达的机制，因此为未来OCIAD2在肿瘤发病机制中的功能分析提供了重要线索。
