Abstract
MicroRNAs (miRNAs) have a major role in cancer pathogenesis, cells growth and apoptosis. We studied the dysregulation of miRNAs after the induction of apoptosis by 4 μM dose of ATO in glioblastoma cell line, U87. The anticancer effect of ATO was verified using MTT, BrdU cell proliferation assay and flow cytometric analysis. Differential expressions of 88 cancer-related miRNAs were analyzed by real-time reverse transcription PCR using miRNA PCR cancer-array system. The fold changes of miRNAs were calculated by comparing the results of treated to untreated control. Among the 88 cancer-related miRNAs, 2-fold upregulation was detected in 26 miRNAs and downregulation in 10 miRNAs compared to the control. The role of some of the miRNAs with significant changes was investigated by searching the literature and studying their roles in apoptosis, cell cycle and in various cellular signalling pathways. Our results showed that ATO modified the expression of a significant number of cancer-related miRNAs in glioblastoma cell line; most of these especially the upregulated miRNAs, were known as tumor suppressors with extensive roles in cancer associated processes and pathways. This study supports the mediatory role of miRNAs in anticancer effect of ATO.
Keywords: Apoptosis, arsenic trioxide, cancer, glioblastoma, microRNA, profiling.
Graphical Abstract