Human uterine leiomyomas (ULMs) are the most common neoplasms in women of reproductive age. The lifetime incidence of this disease is estimated at 70-80%. Approximately 20% of patients with ULMs experience unbearable clinical symptoms resulting in 200,000 hysterectomies annually in the U.S. Although the cause of the disease is unknown, genetic alterations and changes in gene expression have been found in ULMs. We hypothesized that the changes in gene expression associated with ULMs may be due to abnormal expression of microRNAs (miRNAs). To study this, we examined global miRNA expression in 55 ULMs and matched myometrium from 41 patients using a miRNA microarray. Of 206 miRNAs examined, 45 miRNAs were significantly up- or down-regulated in ULMs when compared to the matched myometrium (P < 0.001). The most highly dysregulated miRNAs were the let-7 family, miR-21, miR-23b, miR-29b, and miR-197. Four polycistronic clusters of miRNAs were either up- or down-regulated, in a consistent pattern, indicative of coordinated regulation of these miRNAs. Further analysis revealed that subsets of miRNAs were strongly associated with tumor size and racial background. Using prediction algorithms, we identified potential targets of these miRNAs, some of which had been previously identified as dysregulated in ULMs. One of these, HMGA2 a potential target of the let-7 family of miRNAs and was found to be overexpressed in many ULMs and could be suppressed by let-7 in vitro.
Wang, T., Zhang, X.A., Obijuru, L., Laser, J., Aris, V., Lee, P., Mittal, K., Soteropoulos, P. and Wei, J.J. (2007) MicroRNA Signature Associated with Race, Tumor Size and Target Gene Activity in Human Uterine Leiomyomas. Genes, Chromosomes and Cancer 46, 336-347.
During lung infection Mycobacterium tuberculosis resides inside macrophages and subverts the bactericidal mechanisms of these professional phagocytes. Comprehension of this host-pathogen relationship is fundamental for the development of new therapies to cure and prevent tuberculosis. In this project we compared the gene expression profiling of M. tuberculosis strain H37Rv and a mutant strain with a deletion of the Sigma factor E (SigE) after infection of human macrophage-like cells (THP-1). We conversely analyzed the gene expression profiles of the THP1-1 cells and resting and IFN-gamma treated mouse bone marrow macrophages after infection with the sigE mutant or the wild type strain H37Rv. We were able to conclude that the gene expression profile of M. tuberculosis inside THP-1 cells suggests the perturbation of the cell envelope is one of the major intracellular stresses inside THP-1 macrophages, and that SigE controls the expression of Mtb factors related to maintenance of cell envelope function. We also determined that inflammatory response of both, the THP-1 cells and the mouse bone marrow macrophages was enhanced after infection with the sigE mutant strain as compared to the wild type strain. Our results demonstrate that the Mtb sigma factor E regulates the expression of bacterial components important for the maintenance of the cell envelope that helps the microorganism to cope with environmental stress and to suppress the host immune system and the antibacterial response.
Fontán, P., Aris, V., Ghanny, S., Soteropoulos, P. and Smith, I. (2008) The global transcriptional profile of Mycobacterium tuberculosis during THP-1 human macrophage infection. Infect. Immun. 76:717-25.
Fontán, P.A., Aris, V., Alvarez, M.E., Ghanny, S., Cheng, J., Soteropoulos, P., Trevani, A., Pine, R. and Smith, I. (2008) Mycobacterium tuberculosis SigE Regulon Modulates the Host Inflammatory Response. Journal of Infectious Diseases In Press.
- MicroRNA Profiling in Uterine Leiomyomas
- Transcriptional Profiling of Mycobacterium tuberculosis
- Human Cytomegalovirus Microarray
