1. Differences of immune disorders between Alzheimer’s disease and breast cancer based on transcriptional regulation
- Author
-
Jin Deng, Benteng Di, Xiaoyang Mou, Shuaiqun Wang, Weiming Zeng, Wei Kong, Yang Yang, and Ruxing Zhong
- Subjects
0301 basic medicine ,Male ,Transcription, Genetic ,lcsh:Medicine ,Gene Expression ,Apoptosis ,Disease ,Biochemistry ,Transcriptional regulation ,Medicine and Health Sciences ,lcsh:Science ,Immune Response ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Aged, 80 and over ,Multidisciplinary ,Cell Death ,Neurodegenerative Diseases ,Middle Aged ,Acquired immune system ,Neurology ,Cell Processes ,Female ,Research Article ,Adult ,Immunology ,DNA transcription ,Breast Neoplasms ,Computational biology ,Biology ,03 medical and health sciences ,Immune system ,Protein Domains ,Alzheimer Disease ,Mental Health and Psychiatry ,DNA-binding proteins ,medicine ,Genetics ,Humans ,Gene Regulation ,Aged ,Innate immune system ,Mechanism (biology) ,lcsh:R ,Cancer ,Biology and Life Sciences ,Proteins ,Cell Biology ,medicine.disease ,030104 developmental biology ,Gene Expression Regulation ,lcsh:Q ,Dementia - Abstract
Although chronic inflammation and immune disorders are of great importance to the pathogenesis of both dementia and cancer, the pathophysiological mechanisms are not clearly understood. In recent years, growing epidemiological evidence and meta-analysis data suggest an inverse association between Alzheimer's disease (AD), which is the most common form of dementia, and cancer. It has been revealed that some common genes and biological processes play opposite roles in AD and cancer; however, the biological immune mechanism for the inverse association is not clearly defined. An unsupervised matrix decomposition two-stage bioinformatics procedure was adopted to investigate the opposite behaviors of the immune response in AD and breast cancer (BC) and to discover the underlying transcriptional regulatory mechanisms. Fast independent component analysis (FastICA) was applied to extract significant genes from AD and BC microarray gene expression data. Based on the extracted data, the shared transcription factors (TFs) from AD and BC were captured. Second, the network component analysis (NCA) algorithm in this study was presented to quantitatively deduce the TF activities and regulatory influences because quantitative dynamic regulatory information for TFs is not available via microarray techniques. Based on the NCA results and reconstructed transcriptional regulatory networks, inverse regulatory processes and some known innate immune responses were described in detail. Many of the shared TFs and their regulatory processes were found to be closely related to the adaptive immune response from dramatically different directions and to play crucial roles in both AD and BC pathogenesis. From the above findings, the opposing cellular behaviors demonstrate an invaluable opportunity to gain insights into the pathogenesis of these two types of diseases and to aid in developing new treatments.
- Published
- 2017