Downregulation of miR-485-3p promotes proliferation, migration and invasion in prostate cancer through activation of TGF-ß signaling.

BACKGROUND: Prostate cancer (PC) is the second leading cause of cancer-related death among men worldwide. Downregulation of miR-485-3p has been revealed to participate in the tumorigenesis and progression of many types of cancer. However, the clinical and biological role of miR-485-3p in PC remains largely unknown. METHODS: The expression of miR-485-3p was analyzed in the published databases and detected in our clinical samples and cell lines by RT-qPCR assay. CCK8, transwell invasion and migration, and colony formation assays were performed to investigate the biological function of miR-485-3p. Bioinformatical analysis, RIP, western blotting and luciferase reporter assays were carried out to explore the downstream mechanism of miR-485-3p. RESULTS: The level of miR-485-3p was downregulated in PC tissues, particularly in primary PC tissues with metastasis relative to normal prostate tissues. miR-485-3p downregulation was positively correlated with poor disease-free and overall survival in patients with PC. Functionally, miR-485-3p overexpression dramatically suppressed the proliferation, migration and invasion ability of PC cells in vitro. Mechanistically, miR-485-3p overexpression suppressed the activity of TGF-ß signaling by targeting TGFBR2 to play tumor-suppressive roles in PC progression. CONCLUSION: Our study reports the miR-485-3p/TGFBR2/ TGF-ß signaling axis in tumor development of PC, suggesting miR-485-3p may be a potential target to develop therapeutic strategies against PC.

Long non-coding RNA CRNDE regulates the growth and migration of prostate cancer cells by targeting microRNA-146a-5p.

The function of lncRNA CRNDE and its role in prostate cancer (PC) remains unclear. The aim of this study was to determine the expression level of lncRNA CRNDE in PC tissues and to elucidate its role in PC. The expression levels of lncRNA CRNDE were measured by quantitative reverse transcription polymerase chain reaction. The role of lncRNA CRNDE in PC cells was studied using loss-of-function assays in vitro. Cell proliferation, migration, invasion, and apoptosis were assessed via Cell Counting Kit-8, colony formation, flow cytometry, wound healing, and transwell chamber assays. A luciferase reporter assay was used to characterize the interaction between lncRNA CRNDE and miR-146a-5p. In PC tissues, the expression level of lncRNA CRNDE was upregulated. Moreover, knockdown of lncRNA CRNDE suppressed PC cell proliferation and migration and induced apoptosis in vitro. miR-146a-5p was verified as a direct target of lncRNA CRNDE. Moreover, the inhibition of miR-146a-5p partially counteracted the effects of lncRNA CRNDE on PC cell proliferation, migration, and invasion. In conclusion, lncRNA CRNDE may serve as a cancer promoter in PC by targeting miR-146a-5p. Therefore, lncRNA CRNDE could be a promising target for the clinical treatment of PC.

A microfluidic system based on the monoclonal antibody BCMab1 specifically captures circulating tumor cells from bladder cancer patients.

Circulating bladder tumor cells provide significant information for cancer diagnosis, tumor staging and personalized cancer therapy. Previous studies have reported various methods for capturing circulating tumor cells; however, capturing circulating tumor cells remain a challenge. Here, we present a microfluidic chip with high specificity and capture yields that we refer to as a bladder cancer diagnosis chip. We show that this chip can be used to effectively capture circulating bladder cancer cells based on antibody-BCMab1, a monoclonal antibody that binds to aberrantly glycosylated integrin a3b1. This capture platform is composed of a polydimethylsiloxane (PDMS) chip, whose microchannels are functionalized with biotinylated BCMab1. To change the direction of flow to increase cell-substrate contact, we also introduced a herringbone or chevron channel pattern into the chip. Using this system, we were able to capture bladder cancer cells with high specificity. The capture rates of the bladder cancer diagnosis chip were evaluated at different flow rates and cell concentrations. We found that 90% of the cancer cells were successfully captured at flow rates of 10 µL/min and at various cell concentrations. This highly specific microfluidic chip is a novel tool for bladder cancer diagnosis and offers an opportunity for personalized treatment.

In Situ Mannosylated Nanotrinity-Mediated Macrophage Remodeling Combats Candida albicans Infection.

Deep Candida albicans infection is one of the major causes of death in immunosuppressed hosts. Remodeling macrophages to phenotype M1 can decrease fungus burden and facilitate combating C. albicans under an immunosuppressive state. In this study, a nanotrinity was exploited to direct fungicidal macrophage polarization by leveraging the regulation pathways in macrophage redifferentiation. Conventional chemotherapeutic imatinib, which can abrogate M2 macrophage polarization via "shutting off" the STAT6 phosphorylation pathway, was encapsulated in biodegradable polymeric nanoparticles. In house-customized dual functional mannosylated chitosan oligosaccharides were then coated on the surface of the imatinib-laden nanoparticles, and thus, a mannosylated nanotrinity was achieved with ternary functions for macrophage remodeling: (i) imatinib-blocked STAT6 phosphorylation pathway for decreasing M2 macrophage population; (ii) chitosan oligosaccharides-mediated TLR-4 pathway activation that could promote macrophage redifferentiation to M1 phenotype; (iii) mannose motif-enhanced macrophage targeting. After physiochemical characterization, regulatory effects of the mannosylated nanotrinity on macrophages and the anti-C. albicans efficacy were evaluated at the cellular level and animal level, respectively. The results demonstrated that our mannosylated nanotrinity could efficiently induce macrophage polarization toward the M1 phenotype, decrease M2 phenotype production, and markedly lessen fungus burden and increased the median survival time of mice infected with C. albicans. Therefore, the mannosylated nanotrinity developed in this study could significantly induce macrophage remodeling in situ by the two-pronged process, "turning on" M1 phenotype polarization meanwhile "shutting off" M2 phenotype polarization, and thus allowed to eradicate C. albicans infection.

lncRNA SLCO4A1-AS1 promotes growth and invasion of bladder cancer through sponging miR-335-5p to upregulate OCT4.

BACKGROUND: Bladder cancer (BC) is among the most frequently occurring cancer types in the urinary system. In recent years, the importance of lncRNAs in BC has been acknowledged. SLCO4A1-AS1 is an oncogene in colorectal cancer. However, the role of SLCO4A1-AS1 in BC remains unknown. MATERIALS AND METHODS: The expression levels of SLCO4A1-AS1 in BC tissues were analyzed by qRT-PCR. The effects of SLCO4A1-AS1 knockdown on proliferation were determined by CCK8 assay. Transwell assay was used to evaluate the role of SLCO4A1-AS1 on migration and invasion. Furthermore, xenograft assay was utilized to test the effect of SLCO4A1-AS1 on BC growth in vivo. RESULTS: SLCO4A1-AS1 expression was more upregulated in BC tissues than in adjacent normal tissues. Moreover, SLCO4A1-AS1 level was positively correlated with the advanced stage and metastasis in BC. The upregulation of SLCO4A1-AS1 indicates poor prognosis in BC patients. The knockdown of SLCO4A1-AS1 downregulated the proliferation, migration, and invasion of EJ and T24 cells in vitro. In addition, the loss of SLCO4A1-AS1 prevented BC growth in vivo. Mechanistic investigation showed that SLCO4A1-AS1 was the sponge for miR-335-5p, and miR-335-5p modulated OCT4 expression. CONCLUSION: High SLCO4A1-AS1 expression level was associated with the progression of BC, and SLCO4A1-AS1 promoted the malignant phenotypes of BC cells through the miR-335-5p/OCT4 axis.

Primary Mucinous Adenocarcinoma of Appendix Invading Urinary Bladder with a Fistula: A Case Report.

An adenocarcinoma of the appendix invading the urinary bladder, which is difficult to be diagnosed before the operation, is an extremely rare disease. Only a few cases have been reported. Here we reported a case of patient diagnosed with the mucinous adenocarcinoma of the appendix invading the urinary bladder. The case reported in this study was a 54-years old man who was admitted due to a 6-month history of intermittent episodes of irritative voiding symptoms of the bladder, and weight loss. The patient did not have any gastrointestinal symptoms. The physical examination, laboratory examination, cytology of the urine, computed tomography and cystoscopy were inconclusive. The partial cystectomy, subsequent exploratory laparotomy and intraoperative frozen analysis revealed the appendiceal mucinous adenocarcinoma with a fistula to the urinary bladder. The appendectomy and the right hemicolectomy with a ileocolic anastomosis, the lymphadenectomy and the partial cystectomy limited to the anterior wall was performed. Six months after operation, the patient was in a good health with no obvious discomfort, no recurrence or distant metastases. The recommended treatment for the adenocarcinoma of the appendix invading the bladder with a fistula formation is as follows: appendectomy, right hemicolectomy with ileocolic anastomosis, lymphadenectomy, partial cystectomy and intraperitoneal hyperthermic chemoperfusion.

lncRNA ROR promotes the proliferation of renal cancer and is negatively associated with favorable prognosis.

Renal cell carcinoma (RCC) is one of the third most common types of urological cancer worldwide. Long non­coding RNA (lncRNA) ROR has been reported to be important in regulating the malignant activities of different types of cancer, however, the function of lncRNA ROR in RCC remains to be fully elucidated. In order to investigate the function of lncRNA ROR in RCC, reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis was used to detect the expression of lncRNA ROR in renal cancer tissues and adjacent tissues. Cell proliferation and apoptosis were determined using Cell Counting Kit-8 and apoptosis assays. Western blot analysis was used to measure the expression levels of c­Myc and p53 following the suppression of lncRNA ROR in RCC cell lines. According to the results of the RT­qPCR analysis, lncRNA ROR was found to be expressed at high levels in RCC tissues and cell lines. Patients with RCC exhibiting high expression levels of lncRNA ROR had shorter survival rates, compared with those with low expression levels of lncRNA ROR. The knockdown of lncRNA ROR resulted in a decrease of cell proliferation and increase of apoptosis in vitro. The suppression of lncRNA ROR also induced an increase in the expression of p53 and a decrease in the expression of c­Myc in vitro. Taken together, these results demonstrated that lncRNA ROR was expressed at high levels in RCC tissue and cell lines, and was associated with the proliferation ability of RCC cells. These findings indicate that lncRNA ROR may be a promising therapeutic target for treating RCC.

Upregulation of miR-556-5p promoted prostate cancer cell proliferation by suppressing PPP2R2A expression.

The prognosis and survival rate of prostate cancer are very poor. Previous studies have shown that miR-556-5p have emerged as important regulators in cancer cell biological processes. The role of miR-556-5p in prostate cancer remains unclear. In this study, expression of miR-556-5p in prostate cancer cell lines and tissues was upregulated. Result of MTT assays, colony formation and anchorage-independent growth assays demonstrated that overexpression of miR-556-5p promoted prostate cancer cell growth. Additionally, PPP2R2A was identified as a direct target of miR-556-5p. Ectopic expression of miR-556-5p led to downregulation of PPP2R2A protein, which resulted in the downregulation of p27, upregulation of cyclin D1. Taken together, our data provide compelling evidence that miR-556-5p functions as an onco-miRNA and participates in prostate cancer carcinogenesis by suppressing PPP2R2A expression.

Case report: living donor liver transplantation for giant hepatic hemangioma using a right lobe graft without the middle hepatic vein.

Hepatic hemangioma patients with Kasabach-Merritt syndrome have reportedly been cured by liver transplantation. However, liver transplantation as a potential cure for a stable patient without Kasabach-Merritt syndrome remains debatable. We report the case of a 27-year-old female patient with a giant hepatic hemangioma. The hemangioma measured 50×40×25 cm in size and weighed 15 kg, which is the largest and heaviest hemangioma reported in the literature. The patient showed jaundice, ascites, anemia, and appetite loss; but no disseminated intravascular coagulation was observed through laboratory findings. We successfully operated using a right lobe graft without the middle hepatic vein from a 55-year-old donor. At the long-term follow-up, the patient experienced two acute rejections, which were confirmed by biopsy. However, the patient still survives with good graft function after 50 months.

A new RNA-seq method to detect the transcription and non-coding RNA in prostate cancer.

Prostate cancer is a big killer in many regions especially American men, and this year, the diagnosed rate rises rapidly. We aimed to find the biomarker or any changing in prostate cancer patients. With the development of next generation sequencing, much genomic alteration has been found. Here, basing on the RNA-seq result of human prostate cancer tissue, we tried to find the transcription or non-coding RNA expressed differentially between normal tissue and prostate cancer tissue. 10 T sample data is the RNA-seq data for prostate cancer tissue in this study, we found the differential gene is TFF3-Trefoil factor 3, which was more than seven fold change from prostate cancer tissue to normal tissue, and the most outstanding transcript is C15orf21. Additionally, 9 lncRNAs were found according our method. Finally, we found the many important non-coding RNA related to prostate cancer, some of them were long non-coding RNA (lncRNA).

The rs1050450 C > T polymorphism of GPX1 is associated with the risk of bladder but not prostate cancer: evidence from a meta-analysis.

Glutathione peroxidase (GPX) is an endogenous antioxidant enzyme counteracting oxidative stress. Accumulating evidence has demonstrated that the GPX1 rs1050450 C > T polymorphism may modulate cancer risk, but the association of GPX1 rs1050450 polymorphism with bladder cancer (BC) and prostate cancer (PCa) is still inconclusive. This meta-analysis was designed to determine the exact association of GPX1 rs1050450 C > T polymorphism with the risk of bladder cancer and prostate cancer. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated to estimate the association strength. Databases of PubMed, EMBASE, and China National Knowledge Infrastructure were searched to retrieve eligible studies. In total, ten eligible studies with 6,194 participants were included. By pooling all eligible studies, we found that carriers of the variant T allele were associated with a significantly increased risk of urinary tract cancer (T vs. C: OR = 1.459 and 95% CI, 1.086-1.962; CT/TT vs. CC: OR = 1.411 and 95 % CI, 1.053-1.891). In stratified analysis, we observed that the rs1050450 C > T polymorphism was significantly associated with an increased risk of BC (T vs. C: OR = 2.111 and 95% CI, 1.020-4.368; CT/TT vs. CC: OR = 1.876 and 95% CI, 1.011-3.480), while the association was not significant for PCa. Egger's test and Begg's test revealed no publication bias. The present meta-analysis provides evidence that the GPX1 rs1050450 C > T polymorphism leads to an increased risk of BC but not the risk of PCa.

Hepatopoietin Cn reduces ethanol-induced hepatoxicity via sphingosine kinase 1 and sphingosine 1-phosphate receptors.

The hepatic growth factor hepatopoietin Cn (HPPCn) prevents liver injury induced by carbon tetrachloride in rats. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid produced by sphingosine kinase (SphK). S1P and S1P receptors (S1PRs) are involved in liver fibrogenesis and oxidative injury. This work sought to understand the mechanism by which SphK/S1P/S1PRs are involved in the protective effects of HPPCn on ethanol-induced liver injury and fibrosis. Transgenic mice with liver-specific overexpression of HPPCn (HPPCn(liver) (+/+)) were generated. Two ethanol feeding protocols were used to assess the protective effect of HPPCn on acute and chronic liver injury in mice. Specific inhibitors of S1PR1, S1PR2 and S1PR3 and siRNA were used to examine the roles of S1PRs in hepatic stellate cell (HSC) activation and hepatocyte apoptosis. Increased HPPCn expression in transgenic mice attenuated fibrosis induced by ethanol and carbon tetrachloride (CCl4). Treatment with recombinant human HPPCn prevented human hepatocyte apoptosis and HSC activation. JTE-013 or S1PR2-siRNA attenuated the effect of HPPCn on HSC activation induced by tumour necrosis factor-α (TNF-α). Consistent with the effect of N,N-dimethylsphingosine (DMS), suramin or S1PR3-siRNA treatment blocked HPPCn-induced Erk1/2 phosphorylation in human hepatocytes. This study demonstrated that HPPCn attenuated oxidative injury and fibrosis induced by ethanol feeding and that the SphK1/S1P/S1PRs signalling pathway contributes to the protective effect of HPPCn on hepatocyte apoptosis and HSC activation.