BackgroundRenal cell carcinoma (RCC) is one of the leading causes of cancer related mortality worldwide. Increasing evidence has shown that microRNAs function as oncogenes or tumor suppressors in human malignancies, but the roles of miR-203 in human RCC is still unclear.MethodsFirst, quantitative real-time PCR (qRT-PCR) was performed to detect miR-203 expression in renal cancer cell lines and clear cell RCC (ccRCC) specimens. Then, the association of miR-203 expression with clinicopathological features and survival was later analyzed. Finally, the roles of miR-203 in regulation of tumor proliferation, migration, invasion, and target gene expression were further investigated.ResultsOur study showed miR-203 was down-regulated in renal cancer cell lines and ccRCC specimens (P < 0.05). Respectively, the low miR-203 expression in ccRCC specimens was associated with advanced clinical features and poorer prognosis (P < 0.05). miR-203 expression was an independent prognostic marker of overall ccRCC patient survival in a multivariate analysis (P < 0.05). Transient forced expression of miR-203 inhibited renal cancer cell growth and metastasis (P < 0.05). In contrast, down-regulation of miR-203 expression promoted renal cancer cell growth and metastasis (P < 0.05). Mechanistic investigations confirmed FGF2 as a direct target of miR-203, and up-regulation of miR-203 could decrease expression of FGF2. Further investigation showed that ectopic expression of FGF2 partially reversed the inhibition effect of enforced miR-203 expression on the malignant phenotypes of renal cancer cells.ConclusionsOur study suggested that miR-203 could be a potential prognostic marker and functions as a tumor suppressor in human renal cancer by post-transcriptionally targeting FGF2.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6828145701534108.

Curcumin was recently discovered to strengthen immune response through multiple mechanisms. Cytotoxic CD8+ T-cells play a critical role in modulating anticancer immune response, but is severely restricted by T-cell exhaustion. Bladder carcinomas express PD-L1 and can abrogate CD8+ T-cell response. Thus, we hypothesized that bisdemethoxycurcumin, a natural dimethoxy derivative of curcumin, may provide a favorable environment for T-cell response against bladder cancer when used in combination with α-PD-L1 antibody. Immunocompetent C56BL/6 mouse models bearing subcutaneous or lung metastasized MB79 bladder cancer were established to validate this conjecture. We found that bisdemethoxycurcumin significantly increased intratumoral CD8+ T-cell infiltration, elevated the level of IFN-γ in the blood, and decreased the number of intratumoral myeloid-derived suppressor cells. Furthermore, α-PD-L1 antibody protected these amplified CD8+ T-cells from exhaustion, and therefore facilitated the secretion of IFN-γ, granzyme B, and perforin through these CD8+ T-cells. As a result, this combination treatment strategy significantly prolonged survival of intraperitoneal metastasized bladder cancer bearing mice, suggesting that bisdemethoxycurcumin in combination with α-PD-L1 antibody may be promising for bladder cancer patients.

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Our results suggest that both UV and H(2)O(2 )induce the activation of c-Fos/JunD AP-1 complexes resulting in the prevention of cell death. Moreover, UV irradiation-induced increases in c-Fos/JunD expression in primary MEF cells are mediated through the activation of the MAPK/ERK1/2 signalling pathway.