MicroRNAs are endogenous, small (18–25 nucleotides) non-coding RNAs, which regulate genes expression by directly binding to the 3′-untranslated regions of the target messenger RNAs. Emerging evidence shows that alteration of microRNAs is involved in cancer development. MicroRNA-145 is commonly down-regulated in many types of cancer, regulating various cellular processes, such as the cell cycle, proliferation, apoptosis and invasion, by targeting multiple oncogenes. This review aims to summarize the recent published literature on the role of microRNA-145 in regulating tumourigenesis and progression, and explore its potential for cancer diagnosis, prognosis and treatment.
The activation of cavernous local renin-angiotensin system has an important role in pathogenesis of diabetic erectile dysfunction (ED). In our primary study, we found that angiotensin Type 1 receptor blocker improved the erectile function of diabetic rats. Therefore we explored the losartan in clinical treatment for diabetic patients suffering with ED. A total of 124 diabetic patients with ED were included in this study and treated with losartan or tadalafil or losartan plus tadalafil or watch for waiting as control for 12 weeks. Erectile function was assessed by International Index of Erectile Function (IIEF-5) questionnaire, the percentage of positive responses to sexual encounter profile questions 2 (SEP2), 3 (SEP3) and the global assessment question (GAQ). Losartan or tadalafil or losartan plus tadalafil significantly improved the mean IIEF-5 scores, the percentage of successful penetrations (SEP2), the successful intercourse completions (SEP3) and GAQ (Po0.05). The combination of losartan and tadalafil is more effective than the single-use of losartan or tadalafil (Po0.05). The patients with moderate and mild ED had better response rates to losartan than patients with severe ED. This is the first clinical trial in losartan therapy on diabetic patients suffering from ED. Losartan seems to be effective and well-tolerated in diabetic ED patients, especially for mild to moderate ones. The combination therapy of losartan and tadalafil appeared to be more effective than monotherapy. Keywords: angiotensin type 1 receptor blocker; diabetes; erectile dysfunction; losarton; PDE5 inhibitor INTRODUCTION Erectile dysfunction (ED) is a common complication for diabetic patients. The pathogenesis of diabetic ED is multifactorial, involving the neural, vascular, endocrine and metabolic systems. 1,2 The first-line treatment for diabetic ED is phosphodiesterase Type 5 inhibitors. However, the efficacy of phosphodiesterase Type 5 inhibitors on diabetic ED is only about 51 --62%. 3 --5 Therefore, it is necessary to search for more effective medical therapies for this difficult condition.Our previous study showed that the angiotensin II (Ang II) level in the cavernosum of diabetic rats was much higher than that in normal controls. 6 Kifor et al. 7 reported that exogenous Ang II by ICI could terminate spontaneous erection in dogs, whereas administration of losartan, an Ang II receptor antagonist, resulted in smooth-muscle relaxation and erection. The inhibitor of local renin-angiotensin system (RAS) (angiotensinogen, (pro)renin receptor, angiotensin-converting enzyme, and angiotensin Type I (AT1) receptor ) of cavernosum in diabetic rats was obtained by administration of the angiotensin Type 1 receptor blocker (ARB), losartan. 8 Administration of losantan could also regulate human penile smooth muscle tone 9 and HO-1 gene expression 10 and improves erectile function in diabetic rats. 8 ARBs, a class of selective inhibitors of AT1, such as losartan, valsartan and irbesartan, are medications commonly used for cardiovascular diseas...
Increasing evidence shows that dysregulation of microRNAs (miRNAs) is involved in malignant transformation. We investigated the clinical significance of miR-650 and its involvement in chemoresistance to docetaxel. Our results showed that the relative expression level of miR-650 was significantly higher in LAD tissues than in corresponding nontumor tissues and high level of miR-650 expression was found to be significantly associated with high incidence of lymph node metastasis, advanced clinical stage and poor prognosis of LAD patients. Univariate and multivariate analyses indicated that high miR-650 expression was an independent prognostic factor for survival. Also, we found that the level of miR-650 in LAD tissues was correlated with the response of patients to docetaxel-based chemotherapy. Silencing of miR-650 could increase the in vitro sensitivity of docetaxel-resistant LAD cells to docetaxel, while upregulation of miR-650 decreased the sensitivity of parental LAD cells to docetaxel both in vitro and in vivo. Additionally, silencing of miR-650 could enhance the caspase-3-dependent apoptosis, which might be correlated with the decreased ratio of Bcl-2/Bax. Further researches suggested that inhibitor of growth 4 (ING4) was a direct target of miR-650. Downregulated or upregulated ING4 expression could partially rescue the effects of miR-650 inhibitor or mimics in docetaxel-resistant or parental LAD cells. Furthermore, we found that ING4 was upregulated in docetaxel-responding LAD tissues, and its expression was inversely correlated with miR-650. Thus, miR-650 is a novel prognostic marker in LAD and its expression is a potential indicator of chemosensitivity to docetaxel-based chemotherapy regimen.
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