Background: The microRNA (miRNA) miR-200c-3p is involved in the tumorigenesis and progression of a variety of cancers. However, the underlying regulatory role of miR-200c-3p in prostate cancer (PCa) remains unclear. Methods: Online databases including Oncomine, Linkedomics and StarBase were used to investigate the clinical significance of miR-200c-3p, along with associated gene targets. PCa tissues and adjacent normal tissues were used for the detection of miR-200c-3p expression. A lentivirus overexpressing miR-200c-3p was constructed and transfected into PC3 and DU145 cells. Cell formation of proliferation, migration, and invasion were determined by cell viability and colony-formation assay, wound healing assay, and Matrigel invasion assay, respectively. Epithelial-mesenchymal transition (EMT)-associated markers were determined by qRT-PCR and Western blot. A luciferase reporter assay was performed to determine the direct relationship of miR-200c-3p and ZEB2. The tumor-suppressive role of miR-200c-3p was further confirmed by a xenograft tumor model and immunohistochemical (IHC) staining. Results: Online database analyses showed that miR-200c-3p was associated with pathologic T and N stage in PCa, and miR-200c-3p was downregulated in PCa tissues. Overexpression of miR-200c-3p was considered a tumor suppressor and was found to significantly suppress the formation of migration and invasion in PCa cells via repression of E-cadherin-induced EMT. The bioinformatic database indicated that ZEB2 has a significant correlation with miR-200c-3p and was upregulated in PCa tissues. Further, ZEB2 expression was suppressed by the upregulation of miR-200c-3p and was identified as a direct target of miR-200c-3p. In addition, repression of ZEB2 could restore the levels of miR-200c-3p in PCa cells in turn, suggesting a potential negative loop between miR-200c-3p and ZEB2. miR-200c-3p also had an antitumor effect by negatively regulating ZEB2 in a xenograft mouse model. Conclusions: Taken together, the results of our study demonstrated the novel regulatory loop of miR-200c-3/ZEB2 in PCa progression, providing effective therapeutic strategies for PCa in the future.
SummaryThe development of improved vaccines and vaccination strategies against Mycobacterium tuberculosis has been hindered by a limited understanding of the immune correlates of anti-tuberculosis protective immunity. Simple measurement of interferon-c frequency or production per se does not provide adequate prediction of immune protection. In this study, we examined the relationship between T-cell immune responses and protective efficacy conferred by the heterologous vaccination strategy, bacillus Calmette-Gu erin (BCG) prime-Ag85A DNA boost (B/D), in an early challenge mouse model of pulmonary tuberculosis. The results demonstrated that mice vaccinated with the B/D regimen had a significantly reduced bacillary load compared with BCG-vaccinated mice, and the reduction in colony-forming units was associated with decreased pathology and lower levels of inflammatory cytokines in the infected lungs. Further analysis of immunogenicity showed that the superior protection afforded by the B/D regimen was associated with significantly increased frequency of splenic interleukin-2 (IL-2) -producing CD4 T cells and increased IL-2 production when measured as integrated mean fluorescence intensity post-vaccination as well. These data suggest that measurement of elevated frequency of IL-2-producing CD4 T cells or IL-2 production in the spleens of vaccinated mice can predict vaccine efficacy, at least in the B/D strategy, and add to the accumulating body of evidence suggesting that BCG prime-boost strategies may be a useful approach to the control of M. tuberclosis infection.
β-1,4-galactosyltransferase-I (β-1,4-GalT-I) plays a critical role in the initiation and maintenance of peripheral nervous system inflammatory reaction. However, the exact function of β-1,4-GalT-I in the regulation of SCs proliferation and apoptosis remains unclear. In this study, we found that low concentration of tumor necrosis factor-alpha (TNF-α) induced SCs proliferation, while high concentration of TNF-α induced SCs apoptosis. Meanwhile, the expressions of β-1,4-GalT-I, TNFR1, and TNFR2 were changed following. When β-1,4-GalT I overexpression, low concentration of TNF-α-induced SCs proliferation was partially repressed. Concurrently, the activity of ERK1/2 was decreased. While knocking down β-1,4-GalT I expression, high concentration of TNF-α-induced SCs apoptosis was partially rescued. Consistent with this, the activity of P38 and JNK were decreased. We also found anti-TNFR2 antibody suppressed low concentration of TNF-α-induced SCs proliferation, while anti-TNFR1 antibody inhibited high concentration of TNF-α-induced SCs apoptosis. Thus, present data show that β-1,4-GalT I may play an important role in SCs proliferation and apoptosis induced by TNF-α via different signal pathways and TNFR.
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