Long non­coding RNA BCYRN1 promotes prostate cancer progression via elevation of HDAC11.

Prostate cancer is a serious threat to men's health worldwide. While previous studies have demonstrated that long non­coding RNAs (lncRNAs) are closely associated with the initiation and development of several types of cancer, the role of lncRNAs in the progression of prostate cancer remains incompletely understood. In the present study, the lncRNA brain cytoplasmic RNA 1 (BCYRN1) was found to be overexpressed in prostate tumors compared with healthy tissues. Furthermore, the expression of BCYRN1 was found to be associated with Gleason score and lymph node metastasis. It was demonstrated that BCYRN1 silencing using small interfering RNA (siRNA) inhibited the proliferation of prostate cancer cells. The results of the present study indicated the presence of a reciprocal regulatory association between BCYRN1 and microRNA (miR)­939­3p. In addition, it was observed that BCYRN1 directly sponged miR­939­3p to upregulate histone deacetylase 11 (HDAC11) expression in prostate cancer cells. Moreover, transfection of recombinant HDAC11 reversed the inhibition of cell proliferation that was induced by BCYRN1 siRNA. A positive correlation between BCYRN1 and HDAC11 mRNA expression levels was also identified in prostate tumor and healthy tissues. Therefore, the findings of the present study may provide novel insight into the effects of lncRNAs on prostate cancer, and may enable the development of new therapeutic methods for patients with prostate cancer.

Long non-coding RNA FER1L4 inhibits prostate cancer progression via sponging miR-92a-3p and upregulation of FBXW7.

BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) is involved in development of prostate cancer. However, the molecular mechanisms of many lncRNAs in prostate cancer have not been studied yet. METHODS: The lncRNA Fer-1-like protein 4 (FER1L4) expression was explored in prostate tumors and normal prostate tissues by RT-qPCR and bioinformatic analysis. Overexpression of FER1L4 was performed to evaluate its role in prostate cancer cell proliferation and survival. The molecular mechanism of FER1L4 was investigated by dual luciferase reporter assay, RNA pull down assay, western blotting and RT-qPCR. RESULTS: It was found that FER1L4 was lower in prostate cancer tissues than normal tissues. Higher expression of FER1L4 was associated with prostate cancer tissues of early stage (AJCC stage I/II). Overexpression of FER1L4 inhibited cell proliferation and promoted cell apoptosis in prostate cancer cells. Bioinformatic analysis, RT-qPCR, RNA pull down assay and dual luciferase assay showed that FER1L4 upregulated F-box/WD repeat-containing protein 7 (FBXW7) tumor suppressor via sponging miR-92a-3p. Silencing of FBXW7 reversed the cell phenotypes caused by FER1L4 overexpression in prostate cancer cells. CONCLUSION: The data demonstrated that FER1L4, a downregulated lncRNA in prostate cancer, was pivotal for cell proliferation and survival of prostate cancer. The study provided new sights into understanding of the signaling network in prostate cancer and implied that FER1L4 might be a biomarker for patients with prostate cancer.

Matrine Restrains Cell Growth and Metastasis by Up-Regulating LINC00472 in Bladder Carcinoma.

PURPOSE: Bladder Carcinoma (BC) is a malignant carcinoma with a high incidence in masculinity. We preliminarily researched the efficacy and mechanism of matrine (MAT) in T24 and 5637 cells. PATIENTS AND METHODS: CCK-8, flow cytometry, migration and invasion means were adopted to detect cell viability, apoptosis, migratory and invasive potentials. Moreover, LINC00472 expression was changed via transfection assays and was tested by RT-qPCR. Western blot was used for investigating the levels of CyclinD1, p53, Bcl-2, Bax, pro-Caspase-3, Cleaved-Caspase-3, ß-actin, programmed cell death protein 4 (PDCD4) and relate-proteins of cell pathways. Tumor volume and weight were tested via animal experiments. RESULTS: MAT could not affect the growth of SV-HUC-1 cell but MAT promoted tumor cell apoptosis but restrained viability, invasion and migration. Furthermore, LINC00472 was prominently low expressed in BC tissues. MAT positively regulated LINC00472 and transfection with si-00472 could partly reverse the efficacies of MAT. Moreover, MAT enhanced PDCD4 expression by up-regulating LINC00472. Besides, we discovered MAT elevated PTEN but restrained PI3K/AKT proteins. Finally, tumor volume and weight were declined by MAT in vivo via up-regulating LINC00472. CONCLUSION: MAT restrained cell growth and metastasis but promoted PDCD4 expression by up-regulating LINC00472 via restraining PTEN/PI3K/AKT pathway in BC.

Integrated Bioinformatics Analysis of Potential Biomarkers for Prostate Cancer.

The aim was to expound the pathogenesis of prostate cancer and to identify the potentially biomarkers for prostate cancer (PC). DNA methylation microarray data GSE38240 containing 8 prostate cancer metastases and 4 normal prostate samples as well as gene expression profile data GSE26910 containing 6 prostate primary tumors and 6 normal samples were used. Differentially expressed genes (DEGs) and differently methylated sites of PC were screened and the regulatory network was constructed with DEGs-related transcription factors (TFs). The obtained hub genes were subjected to protein-protein interaction network analysis. Enrichment analysis of down-regulated DEGs were performed. Total 351 DEGs including 190 down-regulated and 161 up-regulated genes and 3234 differently methylated sites were identified. In total 69 DEGs-related TFs were found. Regulatory network contained 1301 nodes and 2527 connection pairs and that FOXA1 (forkhead box A1), BZRAP1-AS1 (benzodiazapine receptor associated protein 1 antisense RNA 1) and KRT8 (keratin 8) were the top three nodes of it. The enriched GO terms were mainly biological activity of the blood and cells-related. Total 29 DEGs (such as AGTR1, angiotensin II receptor, type 1) and 57 none-DEGs involved in the PPI network. Biological functions in blood circulation and the involved AGTR1 may play important roles in PC by gene-methylation. Besides, BZRAP1-AS1 may be novel biomarker related with PC.

Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China.

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients.

Microarray analysis of copy-number variations and gene expression profiles in prostate cancer.

BACKGROUND: This study aimed to identify potential prostate cancer (PC)-related variations in gene expression profiles. METHODS: Microarray data from the GSE21032 dataset that contained the whole-transcript and exon-level expression profile (GSE21034) and Agilent 244K array-comparative genomic hybridization data (GSE21035) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and copy-number variations (CNVs) were identified between PC and normal tissue samples. Coexpression interactions of DEGs that contained CNVs (CNV-DEGs) were analyzed. Pathway enrichment analysis of CNV-DEGs was performed. Drugs targeting CNV-DEGs were searched using the Drug-Gene Interaction database. RESULTS: In total, 679 DEGs were obtained, including 182 upregulated genes and 497 downregulated genes. A total of 48 amplified CNV regions and 45 deleted regions were determined. The number of CNVs at 8q and 8p was relatively higher in PC tissue. Only 16 DEGs, including 4 upregulated and 12 downregulated genes, showed a positive correlation with CNVs. In the coexpression network, 3 downregulated CNV-DEGs, including FAT4 (FAT atypical cadherin 4), PDE5A (phosphodiesterase 5A, cGMP-specific), and PCP4 (Purkinje cell protein 4), had a higher degree, and were enriched in specific pathways such as the calmodulin signaling pathway. Five of the 16 CNV-DEGs (e.g., PDE5A) were identified as drug targets. CONCLUSION: The identified CNV-DEGs could be implicated in the progression of human PC. The findings could lead to a better understanding of PC pathogenesis.

WITHDRAWN: MiR-6838 Promotes Growth and Invasion in Bladder Cancer Via Suppression of Rb.

Ahead of Print article withdrawn by publisher..

Erratum: MiR-4295 promotes cell growth in bladder cancer by targeting BTG1.

[This corrects the article on p. 4892 in vol. 8, PMID: 27904689.].

MiR-4295 promotes cell growth in bladder cancer by targeting BTG1.

microRNAs (miRNAs) have been demonstrated to contribute to tumor progression and metastasis, and have been proposed to be key regulators of diverse biological processes. In this study, we report that miR-4295 is deregulated in bladder cancer tissues and cell lines. To characterize the role of miR-4295 in bladder cancer cells, we performed functional assays. The overexpression of miR-4295 significantly promoted bladder cancer cell proliferation, colony formation, and migration. Moreover, its downregulation induced cell cycle arrest and apoptosis of bladder cancer cells. Furthermore, a luciferase reporter assay and rescue experiment indicated that miR-4295 directly targets BTG1 by binding its 3'UTR. In conclusion, these results demonstrate that miR-4295 acts as an oncogene and may be a potential biomarker for bladder cancer diagnosis and treatment.

Improved Noninvasive Bladder Cancer Diagnosis using Urine Sediments and Novel DNA Methylation Biomarker Panels.

BACKGROUND: Aberrant DNA methylation status early in carcinogenesis represents a potential indicator of tumor detection. We would like to establish a DNA methylation biomarker panel for bladder cancer detection in the research. METHODS: Seven candidate genes with known cancer associations were selected for this study. The DNA methylation status of the candidate genes was analyzed by methylation-specific polymerase chain reaction assays to evaluate the relationship between bladder cancer and target gene methylation status in the urine sediments of participants. RESULTS: 112 bladder cancer patients, 10 healthy volunteers, and 17 glandular cystitis patients were enrolled. There were significant differences in the methylation status of p14ARF, RUNX3, RARß, DAPK, and HPP1 between the healthy control, glandular cystitis, and bladder cancer groups (p = 0.027, p < 0.001, p < 0.001, p = 0.030 and p = 0.003, respectively). A panel composed of all five genes with significant methylation differences yielded an area under the receiver-operating characteristic curve (AUC) of 0.936 and had 98.21% sensitivity and 88.89% specificity, while a panel using just two of these genes (RUNX3 and RARP) yielded an AUC of 0.918 with 96.64% sensitivity and 88.89% specificity. Another panel of two genes (p14ARF and HPP1) had 100% specificity, but an AUC of 0.688 and 37.50% sensitivity. CONCLUSIONS: Using the urine of bladder cancer patients and healthy controls, we assessed several novel DNA methylation biomarker panels that demonstrated good bladder cancer detection capability. Based on the results of this study we recommend the RUNX3 and RARß panel as the first choice for bladder cancer detection. In suspicious or difficult to diagnose cases, the p14ARF and HPP1 panel could be used as an additional diagnostic tool due to its high specificity.

Life threatening biphasic adverse reactions to desmopressin: case report and review of the literature.

Treatment with desmopressin diacetate arginine vasopressin (DDAVP) and its withdrawal are associated with side effects. We present a rare case of severe biphasic adverse reactions induced by DDAVP and its withdrawal in a 63-year-old female patient. A lump in the left axillary region was biopsied, and she received DDAVP after surgery. The following day, she lost consciousness, with foaming at the mouth and seizures. Hypotonic encephalopathy was considered. DDAVP was ceased, and she received electrolytes. On day 1, she displayed low blood pressure and increased urine output. She received DDAVP and dopamine as well as electrolytes. The patient was ambulatory on day 7 and was discharged without brain abnormalities on MRI. In conclusion, severe hyponatremia induced by DDAVP and massive polyuria and hypovolemic shock induced by DDAVP withdrawal are life-threatening conditions. This case underlines the need to be vigilant when administering DDAVP and to monitor for any side effects.

Increased expression of SET domain-containing proteins and decreased expression of Rad51 in different classes of renal cell carcinoma.

In the present study, we aimed to examine whether SET domain-containing methyltransferases are up-regulated in different classes of renal cell carcinoma. We immunoblotted against SET domain and quantified the expression of these modular domains. Furthermore, we examined the expression of Rad51, the key protein that confers genomic stability. There was enhanced expression of SET domain-containing histone methyltransferases in whole lysates of all classes of renal carcinoma. In metastatic high grade clear cell carcinoma, this expression was more pronounced. Though we could not demonstrate direct correlation, we showed that epigenetic modification by methylation is associated with decreased genomic translation of Rad51.

Incidence, prevalence, and medical expenditures of classical amyotrophic lateral sclerosis in Taiwan, 1999-2008.

BACKGROUND/PURPOSE: Amyotrophic lateral sclerosis (ALS) is a rare disease, which makes the estimation of incidence and prevalence difficult in Taiwan. This study was conducted to investigate the incidence, prevalence, and medical expenditure of ALS in Taiwan. METHODS: Patients who had at least one service claim either as an outpatient or inpatient between the years 2004 and 2007 and were over 15 years of age with a primary diagnosis of ALS were identified from the National Health Insurance Research Database. Additionally, ALS patients with serious disability database certificates over 15 years of age were included for the calculation of incidence and prevalence between the years 1999 and 2008. Lastly, the total medical expenditure, including ventilator use and riluzole, were reported. RESULTS: In 2006 and 2008, the average annual incidence and prevalence of ALS was 0.51 and 1.97 (per 10(5)), respectively, in Taiwan. The male-to-female ratio of incidence for ALS was 1.67. The average medical expenditure for ALS patients stayed steady at 16-fold greater than the general population of Taiwan in 2008. The percentage of ventilator and riluzole expenditure as a proportion of total medical expense decreased from 55% in 2000 to 33% in 2008. CONCLUSION: The incidence and average medical expenditure of ALS patients remained stable over the years in Taiwan, however, as a proportion of total medical expenses, expenditure on ventilator and riluzole decreased over the study period.

Favorable outcome of cerebral fat embolism syndrome with a glasgow coma scale of 3: a case report and review of the literature.

Prognosis of deep coma caused by cerebral fat embolism syndrome (CFES) is rarely reported. We present a case of fulminant CFES which was induced by long bone fracture, with a Glasgow Coma Scale (GCS) of 3/15. The brain magnetic resonance imaging (MRI) revealed abnormal spotty lesions scattered over both cerebral hemispheres and the posterior fossa. Thirty days later, the patient regained consciousness with a GCS of 15/15.

RNAi targeting of CCR2 gene expression induces apoptosis and inhibits the proliferation, migration, and invasion of PC-3M cells.

Prostate cancer (PCa) is the second most lethal malignancy in men. It has been reported that chemokines, produced by cancer cells, have linked with tumor progression and metastatic spread. We have proven that chemokine (C-C) motif ligand 2 (CCL2) is involved in the growth and invasion of PCa. In this study, we studied whether CC chemokine receptor 2 (CCR2), the receptor of CCL2, also contributes to PCa progression. We constructed the recombinant plasmid pGCsi-CCR2 and investigated the effects of pGCsi-CCR2 on proliferation, apoptosis, migration, and invasion of PC-3M cells. RT-PCR and Western blot assay showed that transfection with the plasmid pGCsi-CCR2 successfully inhibited the CCR2 expression. The cell proliferation rate was significantly slow, and the apoptotic rate was increased in PC-3M cells treated with CCR2-siRNA, indicated by MTT cell viability and TUNEL assay, respectively. As expected, CCR2 knockdown also reduced the migration and invasion of PC-3M cells, as illustrated through wound-healing assay and Transwell assay. The possible molecular mechanism was the regulation of several signal pathways involved in survival, apoptosis, migration, and metastasis. Altogether, the present finding suggests that CCR2 expression is crucial for CCL2-induced proliferation and invasion of PC-3M cells, and CCR2 could also be a promising molecular target for prevention of PCa growth and metastasis.

Glatiramer acetate could be a hypothetical therapeutic agent for neuromyelitis optica.

Neuromyelitis optica (NMO) is characterized by concurrence of optic neuritis and transverse myelitis, which is typically associated with a spinal cord lesion extending three or more vertebral segments. NMO is an inflammatory, demyelinating central nervous system disorder, and although it has a relapsing course in more than 90% of patients, it differs from multiple sclerosis in that it is more severe, usually spares the brain, and is associated with a longitudinally extensive lesion on spinal cord magnetic resonance imaging (MRI). Furthermore, NMO is associated with a highly specific serum marker called anti-aquaporin-4 antibody, which is believed to have a central pathogenetic role in NMO. Treatment with B-cell specific monoclonal antibody (rituximab) and plasma exchanges appears to reduce the severity and frequency of attacks in NMO, and therefore, B-cell autoimmunity as well as a humoral mechanism may be involved in the pathogenesis of NMO. Glatiramer acetate (GA; also known as Copaxone, COP-1) is a synthetic copolymer of a pool of peptides composed of random sequences of four amino acids: glutamine, lysine, alanine, and tyrosine. GA-specific T-helper 1- (Th1) and 2-type (Th2) cells produce brain-derived neurotrophic factor (BDNF), which may affect neuronal survival and myelin repair. GA treatment also leads to sustained augmentation of BDNF, neurotrophin (NT)-3, and NT-4 expression in various brain regions as demonstrated by histological analysis of immunostained brain sections and BDNF elevation after GA treatment on both protein and mRNA levels. GA-Th2 activation may also have a neuroprotective role in the course of NMO. Furthermore, B cells from GA-treated mice suppress experimental autoimmune encephalomyelitis. The pathogenesis of NMO is largely unknown. However, there is some evidence that B-cell autoimmunity, activation of eosinophils, and B-cell activating factor play important roles, based on neurotrophic factors, neuroprotection, anti-inflammation, and B-cell modulation, GA is thus a hypothetic potential treatment agent for NMO.

[Diagnosis and treatment of non-specific granulomatous prostatitis: a report of 32 cases].

OBJECTIVE: To discuss the diagnosis and treatment of non-specific granulomatous prostatitis (NSGP). METHODS: Thirty-two cases of NSGP were diagnosed by puncture biopsy under transrectal ultrasound (TRUS) and treated with antibiotics and other medicines from September, 2000 to May, 2006. RESULTS: Pathomorphologically, NSGP was basically characterized by granuloma with vessels or grand alveoli in the center. The mean follow-up was 24 months. Urination irritation and obstruction were improved. Q(max) was increased to 15.0-24.0 ml/s, and in 3 cases of urinary retention, to 12.0, 14.5 and 16.5 ml/s, respectively. Digital rectal examination (DRE) indicated a reduced size and softened texture of the prostate induration. PSA was decreased to 1.3-11.5 microg/L. Four cases experienced relapse but were cured after retreated. No prostate cancer was observed. CONCLUSION: NSGP can be definitely diagnosed by puncture biopsy under TRUS and effectively relieved by antibiotics with the alpha-receptor blocker. In case of serious obstruction complicated by urinary retention, transurethral electrotomy can be considered.

[Transrectal ultrasound: an applicable diagnostic approach to chronic prostatitis].

OBJECTIVE: To assess the application value of transrectal ultrasound (TRUS) in the diagnosis of chronic prostatitis. METHODS: TRUS and examination of prostatic secretion (EPS) were used in the diagnosis of 3 500 cases of chronic prostatitis from September, 2000 to May, 2006. RESULTS: Lower resonance of the inner gland, low-level echo, uneven echo light spots, incomplete outlines and unsmooth borderlines were found in 2279 cases (65.1%), and the enlarged prostate in 1 084 cases (31.0%), with clear integrated amicula and enhanced echogenic spots at the juncture of the external and inner gland. No obvious changes were noted in 137 cases (4.0%), and in another 391 cases (11.2%) were detected alteration of the acoustic image of cystospermitis and blurred margins and uneven echoes of the seminal vesicle. The WBC count in EPS was < 10/HP in 132 cases (3.8%), 10-19/HP in 2 156 cases (61.6%) and > or =20/HP in 1212 cases (34.6%). CONCLUSION: TRUS, as a diagnostic means for chronic prostatitis, can be easily performed and causes little pain and therefore is readily accepted by patients. Combined with EPS, TRUS can provide more definite diagnostic evidence, and for those who are afraid of pain and reject EPS, it is a desirable alternative in the diagnosis of chronic prostatitis.