ABSTRACT
Using multiple parallel sequencing on Illumina platform, we identified eight microRNAs that showed significant opposite changes of gene expression in cells of the hormone-sensitive LNCaP prostate cancer cell line and in cells of the hormone-resistant DU-145 cell line, in comparison to the microRNA expression in the normal prostate tissue cells. We found that the insulin-like growth factor 1 receptor (IGF1R) gene is a target of five microRNAs whose expression is increased in LNCaP cells and reduced in DU-145 cells.
Subject(s)
Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic/genetics , Hormones/pharmacology , MicroRNAs/genetics , Prostatic Neoplasms/pathology , Receptors, Somatomedin/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Receptor, IGF Type 1ABSTRACT
It was first shown that DNA damage induction in mitomycin C-treated HeLa cells leads to a change in the selection of 5p and 3p microRNA duplex strands in the formation of the RNA-induced silencing complex (RISC).
Subject(s)
DNA Damage/genetics , DNA Damage/physiology , MicroRNAs/genetics , MicroRNAs/metabolism , DNA Damage/drug effects , HeLa Cells , Humans , Mitomycin/toxicity , Nucleic Acid Synthesis Inhibitors/toxicity , RNA-Induced Silencing Complex/drug effects , RNA-Induced Silencing Complex/genetics , RNA-Induced Silencing Complex/metabolismABSTRACT
The dependence of expression of miRNAs and their precursors (pre-miRNAs) on the DNA methylation level in HeLa cells 8 days after mitomycin C treatment was studied. A massive parallel DNA sequencing method was applied to analyze miRNA expression. 5-Azacytidine (DNA methylation inhibitor) was added to the medium 6 days after mutagenic agent exposure. The results indicated that the change in expression for some mature miRNAs (39 of 61) was accompanied by the change in the expression of their pre-miRNAs, while there were no significant changes in the expression of pre-miRNA for other mature miRNAs (22 of 61). The aberrant expression was maintained by 8 of 61 mature miRNAs and 6 of 55 pre-miRNAs in the induced HeLa cells after 5-azacytidine treatment. In addition, the expression of more than 90% of miRNAs, which indicated a significant change in expression after mitomycin C treatment, does not depend or depends slightly on the DNA methylation level in HeLa cells without mitomycin C treatment. The results suggest that mitomycin C induces aberrant DNA methylation which affects maintenance of changes in the miRNA expression in cell generations after mutagen treatment.
