Studies have shown that miR-221 and miR-222 are deregulated in many cancers, including prostate cancer. Nevertheless, the biological role and the underlying mechanisms of miR-221 and miR-222 in the pathogenesis of androgen-independent prostate cancer are still not clear. The proliferation, apoptosis, cell cycle distinction, and migration capacity of prostate cells were determined following transfection of miR-221 or miR-222 inhibitor. The biological impact and regulation of SIRT1 on prostate cancer cells were investigated. MiR-221 and miR-222 were highly expressed in PC-3 cells compared with in LNCap cells. After miR-221 or miR-222 expression was inhibited, the proliferation and migration rates of PC-3 cells decreased and the apoptosis rate increased. Moreover, SIRT1 protein was up-regulated in cells after they were transfected with miR-221 or miR-222 inhibitor. Cells transfected with siSIRT1 showed increased migration and a decreased apoptosis rate, but there was no significant effect on cell proliferation compared with the controls. There was a negative correlation between miR-221 or miR-222 and SIRT1, but no direct target relationship was identified. These data demonstrate that miR-221 and miR-222 are highly expressed in PC-3 cells. Their inhibition leads to reduced cell proliferation and migration and increased apoptosis in prostate cancer cells. These effects are potentially mediated by up-regulation of SIRT1.
DNA-binding and functional assays examined the role played by NF-IL6 in regulation of HIV-1 transcription in human monocyte/macrophages (U937 cells), stimulated with LPS+PMA. When incubated with nuclear extracts from stimulated cells, a region (-189/-147), containing the major NF-IL6-binding sequence and the USF site, interacted selectively with USF1 and USF2. Anti-C/EBPbeta reacted poorly with the complexes produced with the wild-type probe. In contrast, complex formation with NF-IL6 was clearly evident in experiments analyzing a probe containing an insertion in the USF site. In functional assays, increasing concentrations of a decoy against NF-IL6 reduced gene expression from the LTR of the wild-type HIV-1 variant, supporting a critical role for NF-IL6 in regulation of HIV-1 transcription in stimulated monocyte/macrophages. The decoy also reduced gene expression from a deletion construct lacking NF-IL6-binding sequences. The results implied that in LPS+PMA-stimulated monocyte/macrophages, the endogenous NF-IL6 could act via a site-independent pathway in upregulation of HIV-1 transcription. Analysis of a short DNA segment, containing the -189/-147 region, suggested functional interactions of NF-IL6 and USF. In activated cells exogenous NF-IL6 enhanced dramatically gene expression through a short DNA segment containing the NF-kappaB sites, supporting functional interactions of NF-IL6 and NF-kappaB.
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