Wang Fengfeng, Cho William C S, Chan Lawrence W C, Wong S C Cesar, Tsui Nancy B Y, Siu Parco M, Yip S P, Yung Benjamin Y M
Department of Health Technology and Informatics, Hong Kong Polytechnic University, Lee Shau Kee Building, Hung Hom, Kowloon, Hong Kong.
Department of Clinical Oncology, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong.
Biomed Res Int. 2015;2015:459840. doi: 10.1155/2015/459840. Epub 2015 Mar 3.
Gene expression levels change to adapt the stress, such as starvation, toxin, and radiation. The changes are signals transmitted through molecular interactions, eventually leading to two cellular fates, apoptosis and autophagy. Due to genetic variations, the signals may not be effectively transmitted to modulate apoptotic and autophagic responses. Such aberrant modulation may lead to carcinogenesis and drug resistance. The balance between apoptosis and autophagy becomes very crucial in coping with the stress. Though there have been evidences illustrating the apoptosis-autophagy interplay, the underlying mechanism and the participation of the regulators including transcription factors (TFs) and microRNAs (miRNAs) remain unclear.
Gene network is a graphical illustration for exploring the functional linkages and the potential coordinate regulations of genes. Microarray dataset for the study of chronic myeloid leukemia was obtained from Gene Expression Omnibus. The expression profiles of those genes related to apoptosis and autophagy, including MCL1, BCL2, ATG, beclin-1, BAX, BAK, E2F, cMYC, PI3K, AKT, BAD, and LC3, were extracted from the dataset to construct the gene networks.
The network analysis of these genes explored the underlying mechanisms and the roles of TFs and miRNAs for the crosstalk between apoptosis and autophagy.
基因表达水平会发生变化以适应诸如饥饿、毒素和辐射等应激。这些变化是通过分子相互作用传递的信号,最终导致两种细胞命运,即凋亡和自噬。由于基因变异,这些信号可能无法有效传递以调节凋亡和自噬反应。这种异常调节可能导致致癌作用和耐药性。凋亡和自噬之间的平衡在应对应激时变得至关重要。尽管已有证据表明凋亡与自噬之间存在相互作用,但其潜在机制以及包括转录因子(TFs)和微小RNA(miRNAs)在内的调节因子的参与情况仍不清楚。
基因网络是用于探索基因功能联系和潜在协同调节的图形化展示。从基因表达综合数据库(Gene Expression Omnibus)获取了用于慢性髓性白血病研究的微阵列数据集。从该数据集中提取了与凋亡和自噬相关的那些基因的表达谱,包括MCL1、BCL2、ATG、beclin - 1、BAX、BAK、E2F、cMYC、PI3K、AKT、BAD和LC3,以构建基因网络。
对这些基因的网络分析探索了转录因子和微小RNA在凋亡与自噬相互作用中的潜在机制和作用。