Genome-scale microRNA identify small RNA modulators of the effect of berberine on pancreatic cancer cell growth

Abstract

MicroRNAs (miRNAs) are newly identified small RNA molecules up to 22 nucleotides in length. miRNAs have emerged as important regulators of genes involved in many biological processes, including development, cell proliferation and differentiation, apoptosis and metabolism. Disturbance of microRNA expression may play a role in the initiation and progression of certain diseases including cancer. Human cancers commonly exhibit an altered expression profile of miRNAs with oncogenic (miR-21) or tumor-suppressive (miR-34a) activity. Pancreatic cancer is one of the most aggressive human malignancies with an incidence rates almost identical to mortality rates. This discouraging information is due to the lack of improvement in detection and diagnosis strategies and the paucity of breakthroughs in treatment regimens. A successful drug development in this disease continues to be a major challenge. Recently, a microRNA expression signature has been identified that is associated with pancreatic cancer. Berberine is an isoquinoline alkaloid, isolated from Rhizoma coptidis, and reported to have anti-cancer effects in different human cancer cells. There is however, no available information on the effect of berberine on global miRNA expression pattern in pancreatic cancer. Here we carried out a global miRNA-based expression profiling study in order to identify novel molecular miRNA targets mediating the growth inhibitory effects of berberine on pancreatic cancer cells. Among the 59 significantly expressed genes, 14 were significantly up-regulated and 45 were significantly down-regulated in their expression. Our results showed, for the first time, that berberine was able to modulate the miRNA signature of pancreatic cancer cells.