Open AccessIdentification of novel caspase/autophagy‐related gene switch to cell fate decisions in breast cancers
Author(s) -
Fu L.L.,
Yang Y.,
Xu H.L.,
Cheng Y.,
Wen X.,
Ouyang L.,
Bao J.K.,
Wei Y.Q.,
Liu B.
Publication year - 2013
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12005
Subject(s) - autophagy , biology , caspase , microbiology and biotechnology , kinase , microrna , computational biology , caspase 8 , cancer cell , cancer research , deubiquitinating enzyme , mapk/erk pathway , proteases , programmed cell death , apoptosis , cancer , gene , ubiquitin , genetics , biochemistry , enzyme
Objectives Caspases, a family of cysteine proteases with unique substrate specificities, contribute to apoptosis, whereas autophagy‐related genes ( ATG s) regulate cytoprotective autophagy or autophagic cell death in cancer. Accumulating evidence has recently revealed underlying mechanisms of apoptosis and autophagy; however, their intricate relationships still remain to be clarified. Identification of caspase/ ATG switches between apoptosis and autophagy may address this problem. Materials and methods Identification of caspase/ ATG switches was carried out using a series of elegant systems biology & bioinformatics approaches, such as network construction, hub protein identification, microarray analyses, targeted micro RNA prediction and molecular docking. Results We computationally constructed the global human network from several online databases and further modified it into the basic caspase/ ATG network. On the basis of apoptotic or autophagic gene differential expressions, we identified three molecular switches [including androgen receptor, serine/threonine‐protein kinase PAK ‐1 ( PAK ‐1) and mitogen‐activated protein kinase‐3 ( MAPK ‐3)] between certain caspases and ATG s in human breast carcinoma MCF ‐7 cells. Subsequently, we identified micro RNA s (mi RNA s) able to target androgen receptor, PAK ‐1 and MAPK ‐3, respectively. Ultimately, we screened a range of small molecule compounds from DrugBank, able to target the three above‐mentioned molecular switches in breast cancer cells. Conclusions We have systematically identified novel caspase/ ATG switches involved in mi RNA regulation, and predicted targeted anti‐cancer drugs. These findings may uncover intricate relationships between apoptosis and autophagy and thus provide further new clues towards possible cancer drug discovery.