Our previous microarray data showed that microRNA-224 (miR-224) was downregulated in human prostate cancer (PCa) tissues compared with adjacent benign tissues. However, the underlying mechanisms by which miR-224 is involved in PCa remain unclear. In this study, we identified TRIB1 as a target gene of miR-224. Forced expression of miR-224 suppressed PCa cell proliferation, invasion and migration, and promoted cell apoptosis by downregulating TRIB1. Moreover, the expression level of miR-224 in PCa tissues was negatively correlated with that of TRIB1. miR-224 downregulation was frequently found in PCa tissues with metastasis, higher PSA level and clinical stage, whereas TRIB1 upregulation was significantly associated with metastasis. Both miR-224 downregulation and TRIB1 upregulation were significantly associated with poor biochemical recurrence-free survival of patients with PCa. In conclusion, these findings reveal that the aberrant expression of miR-224 and TRIB1 may promote PCa progression and have potentials to serve as novel biomarkers for PCa prognosis.

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BackgroundSOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa).MethodsThe gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa.ResultsThe microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance.ConclusionsOur data offer the convince evidence that the dis-regulation of SOX7, SOX9 and SOX10 may be associated with the aggressive progression of PCa. SOX7 and SOX9 may be potential markers for prognosis in PCa patients. Interestingly, the down-regulation of SOX7 and the up-regulation of SOX9 may be important mechanisms for castration-resistant progression of PCa.