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Bromodomain PHD finger transcription factor (BPTF), a core subunit of nucleosome-remodeling factor (NURF) complex, plays an important role in chromatin remodeling. However, its precise function and molecular mechanism involved in hepatocellular carcinoma (HCC) growth are still poorly defined. Here, we demonstrated the tumor-promoting role of BPTF in HCC progression. BPTF was highly expressed in HCC cells and tumor tissues of HCC patients compared with normal liver cells and tissues. Knockdown of BPTF inhibited cell proliferation, colony formation and stem cell-like traits in HCC cells. In addition, BPTF knockdown effectively sensitized the anti-tumor effect of chemotherapeutic drugs and induced more apoptosis in HCC cells. Consistently, knockdown of BPTF in a xenograft mouse model also suppressed tumor growth and metastasis accompanied by the suppression of cancer stem cells (CSC)-related protein markers. Moreover, the mechanism study showed that the tumor-promoting role of BPTF in HCC was realized by transcriptionally regulating the expression of human telomerase reverse transcriptase (hTERT). Furthermore, we found that HCC patients with high BPTF expression displayed high hTERT expression, and high BPTF or hTERT expression level was positively correlated with advanced malignancy and poor prognosis in HCC patients. Collectively, our results demonstrate that BPTF promotes HCC growth by targeting hTERT and suggest that the BPTF-hTERT axis maybe a novel and potential therapeutic target in HCC.

Introduction Men frequently develop diabetic erectile dysfunction (DMED), as a result of endothelial dysfunction. DMED patients often have reduced efficacy with phosphodiesterase type 5 inhibitors therapy. Aim To determine whether chronic sildenafil administration can modify the impaired vascular endothelial growth factor (VEGF) system and improve the erectile function in rats with diabetic erectile dysfunction. Methods A group of Sprague Dawley rats (n=30) with DMED were induced by intraperitoneal injection of streptozotocin (40 mg/kg) and screened by subcutaneous injection of Apomorphine (100 mg/kg). They were then exposed to either vehicle or sildenafil (prescribed in our hospital, 5 mg/kg and 10 mg/kg, respectively) for 10 weeks. An additional nondiabetic and age-matched control group (n=10) was also allocated and given the routine diet for the same period. Assessments were performed to both groups at 36 hours after the last dose of sildenafil. Penile intracavernous pressure (ICP), mean arterial pressure (MAP), penile tissue morphology, immunohistologic analysis, and Western blot analysis of VEGF, VEGFR1, and eNOS were determined. Main Outcome Measure Functional, morphological, and proteomical changes on penile structures by the chronic Sildenafil (5 mg/kg and 10 mg/kg, respectively) administration were determined. Results A significant increase of ICP, ICP/MAP ratio, and area under the curve were observed in the both groups treated by sildenafil (5 mg/kg and 10 mg/kg, respectively), compared with the DMED rats without receiving Sildenafil. Immunohistochemical staining of their penile tissue showed a decrease in VEGF, VEGFR1, and eNOS staining in the controlled group compared with an improvement in the chronic sildenafil administration group. Western blot analysis demonstrated exactly the same results. Conclusion We demonstrated that daily sildenafil administration can restore the impaired VEGF system in the penis of DMED rats and progressively improve both erectile function and endothelial function, suggesting a potential general mechanism of improved signaling through the VEGF/eNOS signaling cascade.

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BackgroundInsulin resistance (IR) triggers endothelial dysfunction, which contributes to erectile dysfunction (ED) and cardiovascular disease.AimTo evaluate whether IR was related to ED in young adult patients.MethodsA total of 283 consecutive men complaining of ED at least six months were enrolled, with a full medical history, physical examination, and laboratory tests collected. Quantitative Insulin Sensitivity Check Index (QUICKI) was used to determine IR. The severity of ED was assessed by IIEF-5 questionnaire. Endothelial function was assessed by ultrasonographic examination of brachial artery flow mediated dilation (FMD).ResultsIR was detected in 52% patients. Subjects with IR had significant higher total cholesterol, triglycerides, low density lipoprotein-cholesterol (LDL-c), glycated haemoglobin (HBA1c), high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI), but showed significant lower IIEF-5 score, FMD%, high density lipoprotein -cholesterol (HDL-c), testosterone, sex hormone binding globulin (SHBG) levels than patients without IR. Multiple regression analysis showed QUICKI and testosterone were independent predictors of IIEF-5 score. Furthermore, the incidence of IR was correlated with the severity of ED.ConclusionsCompared with other CVFs, IR was found as the most prevalent in our subjects. Besides, IR was independently associated with ED and its severity, suggesting an adverse effect of insulin resistance on erectile function.