Ovarian cancer is the leading cause of death in women worldwide. Cisplatin is the core of first-line chemotherapy for patients with advanced ovarian cancer. Many patients eventually become resistant to cisplatin, diminishing its therapeutic effect. MicroRNAs(miRNAs) have critical functions in diverse biological processes. Using miRNA profiling and polymerase chain reaction validation, we identified a panel of differentially expressed miRNAs and their potential targets in cisplatin-resistant SKOV3/DDP ovarian cancer cells relative to cisplatin-sensitive SKOV3 parental cells. More specifically, our results revealed significant changes in the expression of 13 of 663 miRNAs analyzed, including 11 that were up-regulated and 2 that were down-regulated in SKOV3/DDP cells with or without cisplatin treatment compared with SKOV3 cells with or without cisplatin treatment. miRNA array and mRNA array data were further analyzed using Ingenuity Pathway Analysis software. Bioinformatics analysis suggests that the genes ANKRD17, SMC1A, SUMO1, GTF2H1, and TP73, which are involved in DNA damage signaling pathways, are potential targets of miRNAs in promoting cisplatin resistance. This study highlights candidate miRNAmRNA interactions that may contribute to cisplatin resistance in ovarian cancer.
Mei LiuXin ZhangChen-Fei HuQing XuHong-Xia ZhuNing-Zhi Xu
The development of cancer is a pathological process involving multiple environmental carcinogenic factors and genetic alterations.For decades,cancer researchers have focused on genomic and transcriptomic analyses.The completion of the Human Genome Project has opened the door to the post-genome era and oncoproteomics.Proteins play a critical role in tumorigenesis and influence the differences between normal cells and malignant cells.This report proposes the concept that cancer is a proteomic disease.This concept is based on examining protein expression profiles,post-translational modifications,and protein-protein interactions in carcinogenesis using recent advances in comparative,functional and structural proteomics.This approach provides a new way of viewing carcinogenesis,presents new clues in biomarker discovery for cancer diagnosis and therapy,and reveals important scientific findings and their significance to clinical applications.
LI GuoQingXIAO ZheFengLIU JianPingLI CuiLI FengCHEN ZhuChu