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microRNAs (miRNAs) are a class of small non-coding RNAs that can post-transcriptionally regulate gene expression and play critical roles in many important biological processes. The role of miRNAs in prostate cancer (PCa) development and pathogenesis remains largely unknown. In the present study, we showed that miR-200b was downregulated in clinical prostatic tumors when compared to normal prostate tissue and in advanced PCa cell lines when compared to normal epithelial prostatic cells. Enforced miR-200b expression suppressed PCa cell proliferation and migration and enhanced chemosensitivity to docetaxel by targeting B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1). Bmi-1 was detected at higher levels in PCa, and knockdown of Bmi-1 showed similar effects as miR-200b overexpression in PCa cells. Moreover, we confirmed that these effects were correlated with increased levels of E-cadherin and P16 and a reduction in vimentin expression and expression of stem cell markers (CD44 and OCT4). These findings suggest that miR-200b plays vital roles as a tumor-suppressor by targeting Bmi-1 and may be a promising therapeutic target for PCa treatment.

Metabonomics is a systematic approach to the study of in vivo metabolic profiles and therefore allows deep insight into and a better understanding of the pathogenesis of disease. To characterize the development of hypertension, a hypertensive animal model, the spontaneously hypertensive rat (SHR), and its normotensive control, the Wistar Kyoto (WKY) rat, were investigated and their blood plasma analyzed using the high-throughput metabolomic tool, gas chromatography/time-of-flight mass spectrometry (GC/TOFMS). A total of 187 peaks were quantitatively determined after deconvolution, and 78 of them were identified. Principal components analysis (PCA) and projection to latent structure partial least-squares discriminant analysis (PLS-DA) were used to process the GC/TOFMS data. The resulting mathematical models were further validated by cross-validation. Plasma compositional differences of many identified compounds showed hypertension-related variation between SHR and WKY rats, and age-related changes from 10 to 18 weeks for both the SHR and WKY rats. These compositional changes involved compounds such as hexadecanoic acid, linoleic acid, oleic acid, stearic acid, 3-hydroxybutyric acid, citric acid, threonic acid, tyrosine, tryptophan, threonine, phenylalanine, serine, ornithine, methionine, 3-hydroxyproline, creatinine, erythrose, myo-inositol, D-methylglucopyranoside, tocopherol, sitosterol, and nonesterified cholesterol. Significantly elevated free fatty acids (FFA) were observed in SHR relative to those in WKY rats, and their levels increased as the SHR aged from 10 to 18 weeks. The close correlation between FFA and hypertension suggests that FFA are potential biomarker candidates for hypertension and they may play an important role in the development of hypertension in SHR. It is also indicated that GC/TOFMS-based metabonomics is a powerful approach to identifying potential biomarkers and investigating the pathological processes of hypertension and the physiological developments of aging.

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