New views and new tools for complex diseases

Abstract

The non-transmittable chronic diseases such as cancer, cardiovascular, metabolic and neurodegeneration diseases already become the major threats to the mankind. All of these chronic diseases are recognized as complex diseases, which involve in multiple genetic factors, environment factors and the interaction of these two kinds of the factors, and the complicated molecular networks consisting of huge number of the genes and proteins. Therefore, it is clear that the conventional experimental biology that focuses on individual gene or protein is not enough to reveal the molecular mechanisms of complex diseases. The collection of six papers in this issue deliver new views to understand the molecular mechanisms of the initiation and progression of the complex diseases, and might provide new powerful tools to fight these diseases. Conventional way often labels particular genes as ‘oncogene’ or ‘tumor suppressor gene’ for their tumorigenic potential. Wu’s group revealed that a famous tumor suppressor gene p53 activated by 5-aza-2 ′ -deoxycytidine (ZdCyd) resulted in high protumorigenicity of mouse P19 embryonic carcinoma cells that are growing in suspension condition, whereas the ZdCyd-induced p53 activation resulted in suppression of tumorigenic potential of P19 EC cells growing on adherent condition. Based on their developed computational method, the authors revealed two different p53-dominant gene-regulatory networks of ZdCyd-treated P19 EC cells at adherent and non-adherent growth conditions, respectively. This study implies that changing cellular contexts of mammalian cells from adherent to non-adherent growth conditions rewires p53-regulating networks that could convert the tumor suppression to tumor-promoting activity. In addition, Auberger’s group reported that Imatinib, an inhibitor of a chimeric tyrosine kinase BCR-ABL, as the leading compound to treat chronic myelogenous leukemia (CML), presented various inhibitory effects on different CML cells. They also found that the variation in the drug effects was derived from different molecular contexts in the CML subpopulations. Regenerative medicine is an important way to treat the chronic diseases such as heart disease, diabetes and Alzheimer’s disease. Stem cells and the related molecular mechanisms of cell reprogramming have been recognized as potential tools for regenerative medicine. Asuelime and Shi reviewed the recent progress on cell-lineage reprogramming and its potential in regenerative medicine. Although the researchers have achieved significant progress, these authors conclude that more studies on this area need to be done before the technology based on lineage reprogramming is ready to the clinical practice. In addition, Kumar’s group in a letter reported that a transcription factor, zinc-finger transcription factor in cerebellum-3 (Zic3), combined with other three transcriptional factors, could induce the conversion of human fibroblasts to neuroprogenitorlike cells in a rapid way; and they suggest that this new approach to reprogramming cells could be a potential tool for screening chemical compounds against neural diseases. Diabetes is a typical age-dependent chronic disease. In this issue, Lammert’s group reported that the up-regulation of an antioxidant protein, DJ-1, in mouse and human islets during aging with non-diabetic conditions, whereas the expression of DJ-1 could be reduced in pancreatic islets of patients with type 2 diabetes mellitus (T2DM). Their further experimental data suggest that DJ-1 might serve as a novel drug target for T2DM. In another paper in this issue, Jia’s group showed that ficolin-3 as an innate immune protein presented a low serum level in the population with insulin-resistance based on a human cross-sectional study. The authors further proposed that serum ficolin-3 could be used as a biomarker for predicting the development of T2DM and even as a potential drugtarget for the treatment of T2DM. We hope that these papers will provide different angles from conventional views to understand the molecular mechanism of complex diseases and new potential tools against these diseases.