Chen Qingchun, Wang Lin, Jiang Minghu, Huang Juxiang, Jiang Zhenfu, Feng Haitao, Ji Zhili
Computation and Systems Biology, School of Electronic Engineering, Beijing University of Posts and Telecommunications, Beijing, China.
Lab of Computational Linguistics, School of Humanities and Social Sciences, Tsinghua University, Beijing, China.
J Cell Physiol. 2018 Feb;233(2):1213-1221. doi: 10.1002/jcp.25988. Epub 2017 Jun 6.
Breast cancer 1 (BRCA1) and E2F transcription factor 1 (E2F1) are related to metabolism and cell cycle regulation. However, the corresponding mechanism is not clear in HCC. High BRCA1 direct pathway was constructed with 11 molecules from E2F1 feedback-interactive network in HCC by GRNInfer based on 39 Pearson mutual positive corelation CC ≥0.25 molecules with E2F1. Integration of GRNInfer with GO, KEGG, BioCarta, GNF_U133A, UNIGENE_EST, Disease, GenMAPP databases by DAVID and MAS 3.0, E2F1 feedback-interactive BRCA1 indirect mitochondrion to cytosol pathway was identified as upstream LAPTM4B activation, feedback UNG, downstream BCAT1-HIST1H2AD-TK1 reflecting protein, and DNA binding with enrichment of small molecule metabolism; The corresponding BRCA1 indirect membrane to cytosol pathway as upstream CCNB2-NUSAP1 activation, feedback TTK-HIST1H2BJ-CENPF, downstream MCM4-TK1 reflecting ATP, and microtubule binding with enrichment of CD4+T-related cell cycle regulation in HCC. Therefore, we propose that E2F1 interactive with BRCA1 pathway induces HCC two different small molecule metabolism or cell cycle regulation via mitochondrion or CD4+T to cytosol. Knowledge analysis demonstrates our E2F1 feedback-interactive BRCA1 pathway wide disease distribution and reflects a novel common one of tumor and cancer.
乳腺癌1（BRCA1）和E2F转录因子1（E2F1）与代谢及细胞周期调控相关。然而，在肝癌中相应机制尚不清楚。基于39个与E2F1具有皮尔逊相互正相关系数CC≥0.25的分子，通过GRNInfer构建了肝癌中由E2F1反馈交互网络的11个分子组成的高BRCA1直接通路。通过DAVID和MAS 3.0将GRNInfer与GO、KEGG、BioCarta、GNF_U133A、UNIGENE_EST、疾病、GenMAPP数据库整合，鉴定出E2F1反馈交互的BRCA1间接线粒体到细胞质通路，其上游为LAPTM4B激活、反馈UNG，下游为BCAT1 - HIST1H2AD - TK1反映蛋白质及DNA结合，且小分子代谢富集；相应的BRCA1间接细胞膜到细胞质通路，上游为CCNB2 - NUSAP1激活、反馈TTK - HIST1H2BJ - CENPF，下游为MCM4 - TK1反映ATP及微管结合，且在肝癌中与CD4 + T相关细胞周期调控富集。因此，我们提出E2F1与BRCA1通路相互作用通过线粒体或CD4 + T到细胞质诱导肝癌两种不同的小分子代谢或细胞周期调控。知识分析表明我们的E2F1反馈交互的BRCA1通路具有广泛的疾病分布，并反映了肿瘤和癌症一种新的共同通路。
