Identification of genes and genetic networks associated with BAG3-dependent cell proliferation and cell survival in human cervical cancer HeLa cells

摘要

Bcl-2-associated athanogene (BAG) 3, is a member of the BAG protein family and a known co-chaperone of heat shock protein (HSP) 70. BAG3 serves a role in regulating a variety of cellular functions, including cell growth, proliferation and cell death including apoptosis. BAG3 is a stress-inducible protein, however the constitutive expression level of BAG3 is increased in cancer cells compared with healthy cells. Recent proteomics technology combined with bioinformatics has revealed that BAG3 participates in an interactome with a number of proteins other than its typical partner HSP70. The functional types represented in the interactome included nucleic acid binding proteins and transcription factors, as well as chaperones, which indicated that overexpression of BAG3 may contribute to proliferation and cell survival through the alteration of gene transcription. While an increasing number of studies have addressed the function of BAG3 as a co-chaperone protein, BAG3-dependent alteration of gene transcription has not been studied extensively. The present study established two BAG3 knockout human cervical cancer HeLa cell clones and addressed the role of BAG3 in cell proliferation and survival through gene transcription, using DNA microarray-based transcriptome analysis and bioinformatics. The present study also identified two genetic networks associated with cellular growth and proliferation' and cell death and survival', which are dysregulated in the absence of BAG3, and may therefore be linked to BAG3 overexpression in cancer. These findings provide a molecular basis for understanding of BAG3-dependent cell proliferation and survival from the aspect of alteration of gene expression.