LncRNA GAS6-AS2 promotes bladder cancer proliferation and metastasis via GAS6-AS2/miR-298/CDK9 axis.

Long noncoding RNAs (lncRNAs) have been proved to play important roles in carcinogenesis and development of numerous cancers, but their biological functions in bladder cancer remain largely unknown. In this study, a novel lncRNA termed GAS6-AS2 were primary identified, and its roles as well as mechanisms in regulating proliferation and metastasis of bladder cancer cells were investigated. Clinically, GAS6-AS2 was significantly up-regulated in bladder cancer tissues and positively correlated with tumour stages and poor prognosis. Moreover, expression of GAS6-AS2 was also increased in bladder cancer cells compared with normal bladder cells. Further investigating the roles of GAS6-AS2, we found GAS6-AS2 regulated proliferation and proliferative activity of bladder cancer cells via inducing G1 phase arrest. What's more, we found that GAS6-AS2 contributed to metastatic abilities of cells. In mechanism, GAS6-AS2 could function as a competitive endogenous RNA (ceRNA) via direct sponging miR-298, which further regulating the expression of CDK9. Finally, we also proved that GAS6-AS2 knockdown suppressed tumour growth and metastasis in vivo. In conclusion, our study proved that GAS6-AS2 could function as a ceRNA and promote the proliferation and metastasis of bladder cancer cells, which provided a novel prognostic marker for bladder cancer patients in clinic.

Identification of recurrence marker associated with immune infiltration in prostate cancer with radical resection and build prognostic nomogram.

BACKGROUND: Some historic breakthroughs have been made in immunotherapy of advanced cancer. However, there is still little research on immunotherapy in prostate cancer. We explored the relationship between immune cell infiltration and prostate cancer recurrence and tried to provide new ideas for the treatment of prostate cancer. METHODS: Prostate cancer RNA-seq data and clinical information were downloaded from the TCGA database and GEO database. The infiltration of 24 immune cells in tissues was quantified by ssGSEA. Univariate Cox regression analysis was used to screen for immune cell types associated with tumor recurrence, weighted gene co-expression network analysis (WGCNA) and LASSO were used to identify hub genes which regulate prognosis in patients through immune infiltration. Then, the nomogram was constructed based on the hub gene to predict the recurrence of prostate cancer, and the decision curve analysis (DCA) was used to compare the accuracy with the PSA and Gleason prediction models. RESULT: Analysis showed that Th2 cells and Tcm related to prostate cancer recurrence after radical prostatectomy, and they are independent protective factors for recurrence. Through WGCNA and Lasso, we identified that NDUFA13, UQCR11, and USP34 involved in the infiltration of Th2 cells and Tcm in tumor tissues, and the expression of genes is related to the recurrence of patients. Based on the above findings, we constructed a clinical prediction model and mapped a nomogram, which has better sensitivity and specificity for prostate cancer recurrence prediction, and performed better in comparison with PSA and Gleason's predictions. CONCLUSION: The immune cells Th2 cells and Tcm are associated with recurrence of PCa. Moreover, the genes NDUFA13, UQCR11, and USP34 may affect the recurrence of PCa by affecting the infiltration of Th2 cells and Tcm. Moreover, nomogram can make prediction effectively.

Transcription factor FoxM1 is the downstream target of c-Myc and contributes to the development of prostate cancer.

BACKGROUND: Prostate cancer is a common malignancy and the second leading cause of cancer death in men. Elevated expression of the transcription factor FoxM1 and c-Myc has been identified in prostate cancer. However, the potential mechanism of elevated FoxM1 and c-Myc to the development of prostate cancer has not been identified. METHODS: In this report, the mRNA level of FoxM1 and c-Myc was detected in 30 prostate cancer and para-cancer tissues. Then, we detected the expression level of FoxM1 by real-time PCR and Western blot after disturbance of the expression level of c-Myc in PC-3 cells. Whether c-Myc could bind to FoxM1 promoter was identified by ChIP assay. Finally, the migratory, invasive, and proliferative abilities in FoxM1 overexpressing and silencing PC-3 cells were detected by wound healing, transwell assay, CCK-8 assays, and Ki-67 protein level. RESULTS: We found that the expression level of FoxM1 and c-Myc were both increased in prostate cancer samples compared with para-cancer samples. The expression level of FoxM1 was changed consistent with the protein level of c-Myc. ChIP assay detected the direct binding of c-Myc in FoxM1 gene promoter. Lastly, overexpression of FoxM1 increased the migratory, invasive, and proliferative abilities of PC-3 cells, and its downregulation significantly decreased the migratory, invasive, and proliferative abilities. CONCLUSIONS: In conclusion, FoxM1 was significantly increased in prostate cancer samples, and it could regulate the proliferative and invasive ability of prostate cancer cells which might be a new target for prostate cancer. Besides, c-Myc could regulate the expression level of FoxM1 by directly binding to its gene promoter.

Anti-tumor and anti-angiogenic effects of Fucoidan on prostate cancer: possible JAK-STAT3 pathway.

BACKGROUND: Prostate cancer is the most common cancer in men in the United States. Fucoidan is a bioactive polysaccharide extracted mainly from algae. The aim of this study was to investigate anti-tumor and anti-angiogenic effects of fucoidan in both cell-based assays and mouse xenograft model, as well as to clarify possible role of JAK-STAT3 pathway in the protection. METHODS: DU-145 human prostate cancer cells were treated with 100-1000 µg/mL of fucoidan. Cell viability, proliferation, migration and tube formation were studied using MTT, EdU, Transwell and Matrigel assays, respectively. Athymic nude mice were subcutaneously injected with DU-145 cells to induce xenograft model, and treated by oral gavage with 20 mg/kg of fucoidan for 28 days. Tumor volume and weight were recorded. Vascular density in tumor tissue was determined by hemoglobin assay and endothelium biomarker analysis. Protein expression and phosphorylation of JAK and STAT3 were determined by Western blot. Activation of gene promoters was investigated by chromatin Immunoprecipitation. RESULTS: Fucoidan could dose-dependently inhibit cell viability and proliferation of DU-145 cells. Besides, fucoidan also inhibited cell migration in Transwell and tube formation in Matrigel. In animal study, 28-day treatment of fucoidan significantly hindered the tumor growth and inhibited angiogenesis, with decreased hemoglobin content and reduced mRNA expression of CD31 and CD105 in tumor tissue. Furthermore, phosphorylated JAK and STAT3 in tumor tissue were both reduced after fucoidan treatment, and promoter activation of STAT3-regulated genes, such as VEGF, Bcl-xL and Cyclin D1, was also significantly reduced after treatment. CONCLUSIONS: All these findings provided novel complementary and alternative strategies to treat prostate cancer.

[Retracted] MicroRNA­136 inhibits prostate cancer cell proliferation and invasion by directly targeting mitogen­activated protein kinase kinase 4.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell migration and invasion assay data shown in Fig. 5C were strikingly similar to data appearing in different form in other articles by different authors at different research institutes, some of which have been retracted. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 4803­4810, 2018; DOI: 10.3892/mmr.2018.8417].

CoFe Alloy-Coupled Mo2C Wrapped by Nitrogen-Doped Carbon as Highly Active Electrocatalysts for Oxygen Reduction/Evolution Reactions.

Molybdenum carbide (Mo2C) with a Pt-like d-band electron structure exhibits certain activities for oxygen reduction and evolution reactions (ORR/OER) in alkaline solutions, but it is questioned due to its poor OER stability. Combining Mo2C with transition metals alloy is a feasible way to stabilize its electrochemical activity. Herein, CoFe-Prussian blue analogues are used as a precursor to compound with graphitic carbon nitride and Mo6+ to synthesize FeCo alloy and Mo2C co-encapsulated N-doped carbon (NG-CoFe/Mo2C). The morphology of NG-CoFe/Mo2C (800 °C) shows that CoFe/Mo2C heterojunctions are well wrapped by N-doped graphitic carbon. Carbon coating not only inhibits growth and agglomeration of Mo2C/CoFe, but also enhances corrosion resistance of NG-CoFe/Mo2C. NG-CoFe/Mo2C (800 °C) exhibits an excellent half-wave potential (E1/2 = 0.880 V) for ORR. It also obtains a lower OER overpotential (325 mV) than RuO2 due to the formation of active species (CoOOH/ß-FeOOH, as indicated by in-situ X-ray diffraction tests). E1/2 shifts only 6 mV after 5000 ORR cycles, while overpotential for OER increases only 19 mV after 1000 cycles. ORR/OER performances of NG-CoFe/Mo2C (800 °C) are close to or better than those of many recently reported catalysts. It provides an interfacial engineering strategy to enhance the intrinsic activity and stability of carbides modified by transition-metals alloy for oxygen electrocatalysis.

Prognostic value of miR-339-5p in patients with prostate cancer and its effects on tumor progression.

Prostate cancer places a serious health burden on males. The present study aimed to explore the potential prognostic significance and biological function of microRNA (miR)-339-5p in patients with prostate cancer. The expression of miR-339-5p was detected in prostate cancer tissues and cell lines by using reverse transcription-quantitative PCR. Kaplan-Meier survival curves and Cox regression analyses were used to investigate the prognostic significance of miR-339-5p in prostate cancer. The Cell Counting Kit-8 assay was used to determine the effect of miR-339-5p on prostate cancer cell proliferation. Transwell assays were used to assess the effect of miR-339-5p on cell migration and invasion. The results indicated that the expression of miR-339-5p was downregulated in prostate cancer tissues and cell lines. Downregulation of miR-339-5p was significantly associated with the Gleason score, lymph node metastasis and TNM stage. Patients with high miR-339-5p expression levels had a longer survival time than those with low expression levels. Multivariate Cox regression analysis indicated that miR-339-5p may be an independent prognostic factor for the overall survival of patients with prostate cancer. Overexpression of miR-339-5p inhibited the proliferation, migration and invasion of prostate cancer cells. Taken together, these results indicated that miR-339-5p functions as a suppressor gene in prostate cancer and acts by inhibiting cell proliferation, migration and invasion of prostate cancer cells. miR-339-5p may serve as an independent prognostic biomarker and therapeutic target for the treatment of prostate cancer.

Corn Stalk-Derived Carbon Quantum Dots with Abundant Amino Groups as a Selective-Layer Modifier for Enhancing Chlorine Resistance of Membranes.

Low permeability and chlorine resistance of normal thin-film composite (TFC) membranes restrict their practical applications in many fields. This study reports the preparation of a high chlorine-resistant TFC membrane for forward osmosis (FO) by incorporating corn stalk-derived N-doped carbon quantum dots (N-CQDs) into the selective polyamide (PA) layer to construct a polydopamine (PDA) sub-layer (PTFCCQD). Membrane modification is characterized by surface morphology, hydrophilicity, Zeta potential, and roughness. Results show that TFCCQD (without PDA pretreatment) and PTFCCQD membranes possess greater negative surface charges and thinner layer-thickness (less than 68 nm). With N-CQDs and PDA pretreatment, the surface roughness of the PTFCCQD membrane decreases significantly with the co-existence of microsized balls and flocs with a dense porous structure. With the variation of concentration and type of draw solution, the PTFCCQD membrane exhibits an excellent permeability with low J(reverse salt flux)/J(water flux) values (0.1-0.25) due to the enhancement of surface hydrophilicity and the shortening of permeable paths. With 16,000 ppm·h chlorination, reverse salt flux of the PTFCCQD membrane (8.4 g m-2 h-1) is far lower than those of TFCCQD (136.2 g m-2 h-1), PTFC (127.6 g m-2 h-1), and TFC (132 g m-2 h-1) membranes in FO processes. The decline of salt rejection of the PTFCCQD membrane is only 8.2%, and the normalized salt rejection maintains 0.918 in the RO system (16,000 ppm·h chlorination). Super salt rejection is ascribed to the existence of abundant N-H bonds (N-CQDs), which are preferentially chlorinated by free chlorine to reduce the corrosion of the PA layer. The structure of the PA layer is stable during chlorination also due to the existence of various active groups grafted on the surface. This study may pave a new direction for the preparation of durable biomass-derivative (N-CQD)-modified membranes to satisfy much more possible applications.

MicroRNA-381 suppresses proliferation and invasion of prostate cancer cells through downregulation of the androgen receptor.

Prostate cancer (PCa) is the most frequently diagnosed malignancy in men and its incidence has increased rapidly worldwide. Notably, the molecular mechanisms underlying prostate tumorigenesis have not been fully identified. The levels of microRNA (miR)-381 have been explored in numerous types of malignancy; however, the expression levels and biological function of miR-381 in PCa remain largely unknown. In the present study, reverse-transcription polymerase chain reaction was used to detect the expression levels of miR-381 in PCa cells and normal prostate epithelial cells. Subsequently, miR-381 antisense oligonucleotides and mimics were transfected into LNCaP PCa cells. Bioinformatics analysis was performed to identify the potential target genes of miR-381. Protein expression analysis, dual-luciferase reporter assay and a rescue assay were used to confirm the target of miR-381. The data suggested that the expression levels of miR-381 were significantly decreased in PCa cells compared with in normal prostatic epithelial cells. Furthermore, transfection of LNCaP cells with miR-381 mimics suppressed their proliferation, migration and invasion. In addition, bioinformatics analysis suggested that the androgen receptor (AR) was a target gene of miR-381. miR-381 suppressed the expression levels of AR by directly binding to its 3'-untranslated region. Furthermore, transfection with an AR plasmid partially attenuated miR-381-induced inhibition of cell proliferation, migration and invasion. The results of the present study suggested that miR-381 may act as a tumor suppressor in PCa by directly targeting the AR.

MicroRNA­136 inhibits prostate cancer cell proliferation and invasion by directly targeting mitogen­activated protein kinase kinase 4.

Prostate cancer (PCa) is the second most common type of cancer and the 6th leading cause of cancer­associated mortality worldwide. Accumulated evidence suggests that PCa initiation and progression are controlled by microRNAs (miRNAs). Therefore, investigating PCa­associated miRNAs may provide novel biomarkers for the diagnosis and treatment of patients with PCa. In the present study it was demonstrated that miRNA­136 (miR­136) expression was significantly downregulated in PCa tissues and cell lines. The resumption of miR­136 expression suppressed cell proliferation and invasion in PCa cells. Bioinformatics analysis predicted that mitogen­activated protein kinase kinase 4 (MAP2K4) was a direct target of miR­136. This prediction was experimentally confirmed by a luciferase reporter assay, RT­qPCR and western blot analysis. MAP2K4 was highly expressed in PCa tissues and inversely correlated with the miR­136 expression level. Additionally, the restoration of MAP2K4 expression significantly blocked the inhibitory effects of miR­136 on cell proliferation and invasion in PCa cells. Therefore, miR­136 may suppress the proliferation and invasion of PCa cells by targeting MAP2K4 and may be a novel candidate target for cancer therapy against PCa.

Alleviatory effects of silicon on the foliar micromorphology and anatomy of rice (Oryza sativa L.) seedlings under simulated acid rain.

Silicon (Si) is a macroelement in plants. The biological effects and mitigation mechanisms of silicon under environmental stress have become hot topics. The main objectives of this study were to elucidate the roles of Si in alleviating the effects on the phenotype, micromorphology and anatomy of the leaves of rice seedlings under acid rain stress. The results indicated that the combined or single effects of Si and simulated acid rain (SAR) stress on rice roots depended on the concentration of Si and the intensity of the SAR stress. The combined or single effects of the moderate concentration of Si (2.0 mM) and light SAR (pH 4.0) enhanced the growth of the rice leaves and the development of the mesophyll cells, and the combined effects were stronger than those of the single treatments. The high concentration of Si (4.0 mM) and severe SAR (pH 3.0 or 2.0) exerted deleterious effects. The incorporation of Si (2.0 or 4.0 mM) into SAR at pH values of 3.0 or 2.0 promoted rice leaf growth, decreased necrosis spots, maintained the structure and function of the mesophyll cells, increased the epicuticular wax content and wart-like protuberance (WP) density, and improved the stomatal characteristics of the leaves of rice seedlings more than the SAR only treatments. The alleviatory effects observed with a moderate concentration of Si (2.0 mM) were better than the effects obtained with the high concentration of Si (4.0 mM). The alleviatory effects were due to the enhancement of the mechanical barriers in the leaf epidermis.

Decreased expression of SLC 39A14 is associated with tumor aggressiveness and biochemical recurrence of human prostate cancer.

OBJECTIVE: Solute carrier family 39, member 14 (SLC39A14), has been identified as a potential biomarker for various cancers. However, its roles in prostate cancer (PCa) are still unclear. The aim of this study was to investigate the clinical significance of SLC39A14 in patients with PCa and its functions in malignant phenotypes of PCa cells. PATIENTS AND METHODS: Subcellular localization and expression pattern of SLC39A14 protein were examined by immunohistochemistry. Then, the associations of SLC39A14 expression with various clinicopathological features and clinical outcome of patients with PCa were statistically evaluated. Subsequently, the effects of SLC39A14 overexpression and knockdown on PCa cell proliferation and motility were, respectively, examined by Cell Counting Kit-8, transwell, and wound-healing assays. RESULTS: The immunoreactive scores of SLC39A14 protein in human PCa tissues were significantly lower than those in normal prostate tissues. Based on the Taylor dataset, SLC39A14 downregulation occurred more frequently in patients with PCa with a higher Gleason score (P<0.001), advanced clinical stage (P=0.008), presence of metastasis (P=0.009), and prostate-specific antigen failure (P=0.006). More interestingly, the survival analysis identified SLC39A14 as an independent factor for predicting the biochemical recurrence-free survival of patients with PCa (P=0.017). Functionally, the enforced expression of SLC39A14 could suppress cell proliferation, invasion, and migration of PCa cell lines in vitro, which could be reversed by the knockdown of SLC39A14. CONCLUSION: Decreased expression of SLC39A14 may lead to malignant phenotypes of PCa cells and aggressive tumor progression in patients with PCa. Importantly, SLC39A14 may function as a tumor suppressor and a biomarker for screening patients with biochemical recurrence following radical prostatectomy.