Microarray profiling of HepG2 cells ectopically expressing NDRG2.

Previous studies have demonstrated that N-Myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor that is downregulated in many human cancers and when overexpressed, can inhibit tumor growth and metastasis. However, its molecular function, its modulatory targets, and signaling pathways associated with it remain unclear. Here, in an effort to identify the genes modulated by NDRG2 expression, a microarray study was conducted to detect the expression profile of HepG2 cells overexpressing NDRG2 or LacZ. Gene Ontology (GO) biological process analysis revealed that genes related to G protein signaling pathway were upregulated. Five of them were selected and verified by real-time PCR. Gene sets related to M phase of cell cycle were downregulated. This was in agreement with cell cycle analysis. Signaling pathway analysis demonstrated apparent augmented hematopoietic cell lineage pathway and cell adhesion, but reduced glycosylphosphatidylinositol (GPI)-anchor biosynthesis, protein degradation and SNARE interactions. Furthermore, through motif analysis and experimental validation, we found that the p38 phosphorylation can be increased by NDRG2. Our research provides the molecular basis for understanding the role of NDRG2 in tumor cells and raises interesting questions about its mechanisms and potential use in cancer therapy.