Identification of gene expression profiles associated with doxorubicin resistance in paired doxorubicin-resistant and doxorubicin-sensitive osteosarcoma cell lines

By investigating the differences in the gene expression patterns among paired doxorubicin-resistant and doxorubicin-sensitive human osteosarcoma cell lines and seeking novel associated genes using a human mRNA microarray, we identified that 3,278 mRNAs (1,607 up-regulated and 1,671 down-regulated) were aberrantly expressed in three sets of doxorubicin-resistant MG63/DXR cells and their corresponding parental MG63 cells (fold-change >2.0, P<0.05 and FDR<0.05). Eleven randomly selected mRNAs were confirmed by qRT-PCR and WB detection in three paired doxorubicin-resistant and doxorubicin-sensitive osteosarcoma cell lines (MG63 vs MG63/DXR, KH-OS vs KH-OS/DXR, U2-OS vs U2-OS/DXR), and the results were consistent with our microarray data. Bioinformatics analysis identified some novel genes and pathways related to the development of chemoresistance, including the RUNDC3B, ADAM22, ARMCX2, CRYAB and NOD-like receptor signaling pathway, the RIG-I-like receptor signaling pathway and more classical genes and pathways such as ABCB1, apoptosis-related pathways, the TNF signaling pathway, and chemokine signaling pathways. In addition, we found that RUNDC3B was distinctly increased in specimens of OS patients with a poor response to chemotherapy and that patients with reduced expression may survive longer than those with elevated expression, which suggests that RUNDC3B may be a possible biomarker to predict chemotherapeutic response and prognosis of osteosarcoma patients. These results provided valuable clues for future studies to discover possible novel targets to combat multi-drug resistance.