LncRNA CASC15 functions as an oncogene by sponging miR-130b-3p in bladder cancer.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA CASC15 functions as an oncogene by sponging miR-130b-3p in bladder cancer, by X. Yu, Z.-L. Wang, C.-L. Han, M.-W. Wang, Y. Jin, X.-B. Jin, Q.-H. Xia, published in Eur Rev Med Pharmacol Sci 2019; 23 (22): 9814-9820-DOI: 10.26355/eurrev_201911_19544-PMID 31799648" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19544.

LncRNA CASC15 functions as an oncogene by sponging miR-130b-3p in bladder cancer.

OBJECTIVE: Recent studies have revealed that long noncoding RNAs (lncRNAs) are dysregulated in malignant tumors and participates in carcinogenesis. The purpose of our study was to uncover the mechanisms underlying lncRNA CASC15 in bladder cancer (BLCA). PATIENTS AND METHODS: In this research, Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to detect cancer susceptibility candidate 15 (CASC15) expression in BLCA samples and cells. Besides, the wound healing assay and transwell assay were performed in BLCA cells after CASC15 was knocked down. Furthermore, the bioinformatics analysis and dual-luciferase reporter assay were conducted to explore the target miRNA of CASC15, which was further verified through rescue experiments in BLCA cells. RESULTS: CASC15 expression was upregulated in BLCA tissue samples. Moreover, CASC15 downregulated the miR-130b-3p expression and promoted cell migration and invasion in BLCA in vitro. The rescue experiments also revealed that the inhibitory effects by the silence of CASC15 could be reversed through the inhibition of miR-130b-3p. CONCLUSIONS: Our study suggested a vital regulatory mechanism of CASC15 in BLCA, and the CASC15/miR-130b-3p axis might serve as a new therapeutic interventional target for BLCA patients.

MicroRNA-373-3p inhibits prostate cancer progression by targeting AKT1.

OBJECTIVE: This study aims to investigate whether microRNA-373-3p could inhibit the progression of prostate cancer (PCa) by targeting and degrading AKT1. PATIENTS AND METHODS: Expression levels of microRNA-373-3p and AKT1 in PCa tissues and benign prostate hyperplasia (BPN) tissues were detected by quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR). According to the follow-up data, survival curves and receiver operating characteristic (ROC) curves were drawn to investigate whether microRNA-373-3p could be served as a biomarker for early diagnosis and prognosis of PCa. The effect of microRNA-373-3p on cell proliferation was examined by cell counting kit-8 (CCK-8) assay. Subsequently, we explored the direct binding condition of AKT1 and microRNA-373-3p by dual-luciferase reporter gene assay and Western blot. RESULTS: QRT-PCR results showed that microRNA-373-3p level was significantly lower in PCa tissues compared with that of BPN tissues, whereas AKT1 expression was significantly increased. By analyzing the survival curve and ROC curve, we found that the overall survival (OS) of PCa patients with higher microRNA-373-3p expression was markedly longer than those with lower expression. Besides, microRNA-373-3p could be used as an early diagnostic marker to distinguish PCa from BPH. Overexpression of microRNA-373-3p in PCa cells (LNCaP and PC3 cells) remarkably inhibited cell proliferation. Dual-luciferase reporter gene assay and Western blot showed that microRNA-373-3p targeted the 3'UTR of AKT1 and inhibited its expression. CONCLUSIONS: Downregulated microRNA-373-3p promoted the proliferation of prostate cancer cells via targeting AKT1.

MicroRNA-212 participates in the development of prostate cancer by upregulating BMI1 via NF-κB pathway.

OBJECTIVE: To investigate the role of microRNA-212 in prostate cancer (PCa) and its underlying mechanism. PATIENTS AND METHODS: MicroRNA-212 expressions in 72 PCa tissues and paracancerous tissues were detected by qRT-PCR (quantitative real-time polymerase chain reaction). The relationship between microRNA-212 expression and clinical characteristics of PCa patients was analyzed. Target genes of microRNA-212 were predicted by TargetScan and verified by luciferase reporter gene assay. Proliferation, cell cycle, and apoptosis of PCa cells were detected after transfection with corresponding plasmids of microRNA-212 in PCa cells, respectively. The effect of microRNA-212 on BMI1 and NF-κB pathway was detected by Western blot. RESULTS: MicroRNA-212 was downregulated in PCa patients. The survival rate of PCa patients with lower expression of microRNA-212 was remarkably lower than those with a higher level. After overexpression of microRNA-212, we observed inhibited proliferation and arrested cell cycle of PCa cells. Increased apoptosis was found after PCa cells were transfected with microRNA-212 mimic. Luciferase reporter gene assay showed that microRNA-212 was bound to BMI1, which further promoted PCa development via NF-κB pathway. CONCLUSIONS: MicroRNA-212 was downregulated in PCa tissues, which could promote the PCa development by targeting BMI1 via NF-κB pathway.

Varicocele is associated with hypogonadism and impaired erectile function: a prospective comparative study.

We conducted this prospective comparative study to examine the hypothesis that varicocele was associated with hypogonadism and impaired erectile function as reflected in International Index of Erectile Function-5 (IIEF-5) scores as well as nocturnal penile tumescence and rigidity (NPTR) parameters. From December 2014 to December 2015, a total of 130 males with varicocele complaining of infertility or scrotal discomfort and 130 age-matched healthy males chosen from volunteer healthy hospital staff as controls were recruited in this study. Serum testosterone (TT) levels and IIEF-5 scores as well as NPTR parameters were evaluated and compared between varicocele and control subjects. All participants were further grouped into hypogonadism based on the cut-off value 300 ng/dL. A total of 45 of 130 patients were identified as hypogonadism, while it was not found in control subjects. A multivariate logistic regression with likelihood ratio test revealed that TT levels as well as grade III and II varicocele posed significant indicators for hypogonadism occurrence (chi-square of likelihood ratio = 12.40, df = 3, p < .01). Furthermore, TT levels and infertility duration were associated with IIEF-5 scores in a multivariate linear regression analysis (adjusted R2  = 0.545). In conclusion, the correlation of grade III and II varicocele with an increased risk of hypogonadism was confirmed in this study and an impaired erectile function correlated with TT levels and infertility duration was also observed.

Berbamine inhibited the growth of prostate cancer cells in vivo and in vitro via triggering intrinsic pathway of apoptosis.

BACKGROUND: Berbamine (BBM) has been reported with antitumor activities. BBM inhibited the growth of prostate cancer (PCa) cells and caused vacuolization of mitochondria in preliminary study. We hypothesized BBM could enhance apoptosis of PCa cells through mitochondrial pathway. METHODS: Growth of PC-3 and LNCaP cells treated by BBM was determined by cell viability assay. The morphology of mitochondria was observed by electron microscopy. Apoptosis was quantified by flow cytometry. Expressions of bax/bcl-2, active caspase-9 and active caspase-3 were examined by western blot and real-time PCR. Methazolamide, an inhibitor of cytochrome c, was added to examine its blockade effect on BBM. PC-3 cells were injected subcutaneously into athymic mice, and BBM or saline was administrated intravenously. Diameters of induced tumors were compared, and ratios of apoptotic cells in tumor tissues were calculated. RESULTS: BBM inhibited viability of cultured PC-3 and LNCaP cells in dose- and time-dependent manners. Flow cytometry showed BBM induced apoptosis in cultured cells. Mitochondria showed swelling, vacuolization and fused mitochondrial cristae. Western blot and real-time PCR analysis both showed increases of bax/bcl-2, active caspase-9 and active caspase-3. Methazolamide impeded effect of BBM on inducing apoptosis of cultured cells, and activations of caspase-9 and caspase-3 were also inhibited. Growth of tumors by grafted PC-3 cells was significantly slower in BBM group. Ratios of apoptotic cells in tumors were significantly higher in BBM group. Expressions of active caspase-9 and active caspase-3 in tumors were significantly upregulated by BBM. CONCLUSIONS: BBM exhibited strong anti-PCa activities in vitro and in vivo relying on activating caspase-3 via intrinsic pathway of apoptosis, holding a great promise to develop new strategies for PCa.

Racial disparities in the association between diabetes mellitus-associated polymorphic locus rs4430796 of the HNF1ß gene and prostate cancer: a systematic review and meta-analysis.

Polymorphism 17q12 rs4430796 within HNF1ß is a genetic variant associated with both diabetes mellitus and prostate cancer, but findings on the correlations of rs4430796 with prostate cancer risk specifically are not in agreement, especially among diverse populations. To shed some light on the contradictory findings, therefore, we carried out a meta-analysis by pooling the odds ratios (ORs) with corresponding 95% confidence intervals (CIs) of all currently available case-control studies located within PubMed and Embase databases up to December 2012. A total of 16 studies comprising 30 datasets that collectively involved 25,535 prostate cancer patients and 25,726 controls were ultimately included in this analysis. The meta-analysis of all the studies revealed that the rs4430796 polymorphism was significantly associated with an increased risk of prostate cancer in all contrast models (ORA vs G = 1.25, 95%CI = 1.21-1.30, POR < 0.001; ORAA vs GG = 1.53, 95%CI = 1.45-1.62, POR < 0.001; ORAG vs GG = 1.24, 95%CI = 1.16-1.34, POR < 0.001; ORAA vs AG+GG = 1.36, 95%CI = 1.30-1.42, POR < 0.001; ORAA+AG vs GG = 1.37, 95%CI = 1.30-1.44, POR < 0.001). After subgroup analyses stratified by ethnicity, however, the rs4430796 polymorphism was significantly associated with prostate cancer in both Caucasians and Asians but not in African-Americans. In conclusion, our meta-analysis identified a significant association between the 17q12 rs4430796 polymorphism and prostate cancer risk, although the degree of this association and frequency of the causative allele varied among men of different races.

Expression of liver-targeting peptide modified recombinant human endostatin and preliminary study of its biological activities.

Recombinant human endostatin (rEndostatin or endostar) has been shown to inhibit endothelial cells proliferation, migration, and angiogenesis and exhibits a broad spectrum of activities against solid tumors. However, rEndostatin is easily degradable and evenly distributed to all tissues. Selectively delivering rEndostatin to the lesion site might be more potent. The circumsporozoite protein (CSP) coats the malarial sporozoite and targets the liver for infection; I-plus of N end of CSP could specifically bind to the liver. Based on this, we hypothesize the fusion protein with introducing the CSP I-plus sequence into rEndostatin (rES-CSP) of which not only targets the liver, but also inhibits endothelial cells proliferation, migration, and tube formation. Therefore, it selectively reduces angiogenesis of hepatocellular carcinoma (HCC) and improves the anti-HCC effect. In this study, we synthesized a novel rES-CSP fusion gene by SOE-PCR and expressed the fusion protein in Escherichia coli BL2l (DE3). The suitable conditions were optimized by an orthogonal test (L(25)(5)(4)). The yields were 12 mg/l culture medium following refolding and purification on nickel-nitrilotriacetic acid (Ni-NTA) metal affinity chromatography matrices. The purified rES-CSP is specifically targeted to the hepatocyte and inhibited the proliferation and migration of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner and showed potent antiangiogenic capability on HUVECs tube formation assay and chick embryo chorioallantoic membrane (CAM) assay. These results lay the foundation for the further study of its targeting and anti-HCC in vivo and provide a feasible and convenient approach to produce liver-targeting drugs for treatment of the liver diseases.

Adenovirus-mediated delivery of soluble ST2 attenuates ovalbumin-induced allergic asthma in mice.

Allergic asthma is associated with excessive T helper type 2 (Th2) cells activation and airway hyperreactivity (AHR), implicated in the context of significant morbidity and mortality. Soluble ST2, a member of the interleukin (IL)-1 receptor family, has been shown to play a critical role in modulation of inflammatory disorders, yet the function of soluble ST2 in allergic inflammation remains unclear. In this study, we examined the possibility of regulating ovalbumin (OVA)-challenged airway inflammation by recombinant adenovirus-mediated sST2-Fc (Ad-sST2-Fc) gene transfer. Single intranasal administration of Ad-sST2-Fc before allergen challenge in OVA-immunized mice profoundly reduced serum immunoglobulin (Ig)E secretion, eosinophil infiltration and concentrations of IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid compared with administration of a control Ad vector. Histopathological examination of the lungs revealed that sST2-Fc over-expression markedly suppressed allergen-induced peribronchial inflammation and disruption of the alveolar architecture. Moreover, the beneficial effect of sST2-Fc in allergic lung inflammation is related to blocking the IL-33/ST2L signalling. Taken together, these results suggested that administration of Ad-sST2-Fc gene transfer may have therapeutic potential for the immunomodulatory treatment of OVA-mediated allergic pulmonary diseases.

Adenovirus-mediated overexpression of soluble ST2 provides a protective effect on lipopolysaccharide-induced acute lung injury in mice.

Acute lung injury is characterized by a diffuse inflammatory parenchymal process, implicated in the context of significant morbidity and mortality. Previously, we have reported that soluble ST2 (sST2), a member of the Toll-interleukin (IL)-1 receptor (TIR) superfamily, represses proinflammatory cytokine production of macrophage exposed to lipopolysaccharide (LPS). In this study, we examined the possibility of modulating LPS-induced murine inflammatory pulmonary damage by recombinant adenovirus-mediated sST2-Fc (Ad-sST2-Fc) gene transfer. Single intranasal administration of Ad-sST2-Fc led to a profound decrease in LPS-induced bronchoalveolar lavage leucocyte exudation and lung tissue myeloperoxidase activity (reflecting phagocyte infiltration). Histological examination revealed alveolitis with inflammatory cell infiltration and alveolar haemorrhage in the alveolar airspace was less severe in Ad-sST2-Fc-treated mice when compared with control groups. In addition, high levels of sST2-Fc in vivo reduced the transcription of tumour necrosis factor-α, IL-6 and Toll-like receptor-4 gene remarkably, and suppressed the nuclear translocation of nuclear factor-κB in lung tissues in response to LPS challenge. Taken together, these results suggested that administration of Ad-sST2-Fc gene transfer may have therapeutic potential for the immunomodulatory treatment of LPS-mediated inflammatory lung injury.

Specific detection and properties of enzyme hydrolyzing phosphonate ester in serum.

An enzyme capable of hydrolyzing 4-methylumbelliferyl phenylphosphonate to 4-methylumbelliferone and phenylphosphonic acid has been detected in human serum. It has a Km value of 1.72 x 10(-4) mol/L, has an optimum pH of 8.8-9.1 in Tris buffer, and shows maximum activity at 60 degrees C (30 min). The enzymic activity can be inhibited by Na3PO4, EDTA, and cysteine. We saw no effect of CuSO4, adenosine, thymidine, NaN3, diethyl p-nitrophenyl phosphate, p-chloromercuribenzoate, isopropyl fluorophosphate, or eserine on the enzymic activity. The enzyme cannot hydrolyze substrates of phosphodiesterase I or alkaline phosphatase. The enzyme is considered a phosphonate esterase.