Selenium nanoparticles inhibit tumor metastasis in prostate cancer through upregulated miR-155-5p-related pathway.

Prostate cancer are the most common, malignant and lethal tumors in men, and the complexity of prostate cancer (CaP) is also due to the diverse metastasis profile. Selenium nanoparticles (SeNPs) have been reported to have potent antitumor activity, but whether it impacted the tumor metastasis is not fully clear. Here, we confirmed that SeNPs could inhibit the CaP cell migrations and invasions. Combined with our previous findings, we identified a series of microRNAs that could be upregulated significantly under SeNP treatment, among which miR-155-5p acts as a key component in mediating the SeNP-inhibited migration and invasion of CaP cells, through directly targeting IκB kinase ɛ and Sma- and Mad-related protein 2. The cell-based results were proved in xenograft mice modeling. These results have evidently signified the antitumor potential of SeNPs in the treatment of prostate cancer.

Selenium nanoparticles (SeNPs) have potent antitumor activity against prostate cancer cells through the upregulation of miR-16.

OBJECTIVES: This research aimed to examine the antitumor mechanisms of selenium nanoparticles (SeNPs) specifically against prostate cancers. METHODS: The antitumor activities of SeNPs against cancer cells were determined via MTT assay. The cell cycle was determined by detecting the DNA content, and apoptosis was determined via annexin V-Fluos staining kit. The microRNA expressions in cancer cells were analyzed via microarray and qRT-PCR. The potential targets of miR-16 were identified via luciferase analysis and mRNA expression determination. miR-16 functions in cancer cells were explored via the transient transfection of miR-16 mimic or inhibitor. RESULTS: SeNPs were most potent in prostate cancer cells, regardless of whether or not they were androgen-dependent. Furthermore, SeNP stimulation can induce cell cycle arrest and the apoptosis enhancement of prostate cancer cells. Microarray and molecular mechanism studies demonstrated that miR-16 could directly target cyclin D1 and BCL-2 to mediate SeNP apoptosis enhancement. Results show that the serum selenium levels positively correlate with miR-16 expressions, and they correlate with the overall and disease-free survival rates. CONCLUSION: These results signify the cytotoxic potential of SeNPs in prostate cancer treatment.

Hand Painting of Noniridescent Structural Multicolor through the Self-Assembly of YOHCO3 Colloids and Its Application for Anti-Counterfeiting.

YOHCO3 colloidal particles with tunable size, composition, and optical properties were prepared, and they were used for the fabrication of amorphous photonic crystals? (APCs) patterns through direct hand painting. YOHCO3 colloids were synthesized by a seeding growth method, in which the colloid size could be controlled by altering the seed amounts and the composition and optical properties can be altered via the doping of Eu3+. APCs? films with bright, permanent, and tunable structural colors were prepared by the self-assembly of YOHCO3 colloids of different sizes. Multicolor patterns can be obtained quickly and efficiently by hand painting with the dispersion of YOHCO3 colloids as ink. An APCs? pattern assembled from YOHCO3:Eu colloids is also fabricated, and the pattern shows blue structural color under natural light and bright red colors under illumination of UV light. The facile synthesis procedure, simple assembly process, and unique optical properties of the APCs make it valuable for practical applications such as structural color-based printing and anticounterfeiting.

MicroRNA-regulated transcriptome analysis identifies four major subtypes with prognostic and therapeutic implications in prostate cancer.

MicroRNA (miRNA) deregulation plays a critical role in the heterogeneous development of prostate cancer (PCa) by tuning mRNA levels. Herein, we aimed to characterize the molecular features of PCa by clustering the miRNA-regulated transcriptome with non-negative matrix factorization. Using 478 PCa samples from The Cancer Genome Atlas, four molecular subtypes (S-I, S-II, S-III, and S-IV) were identified and validated in two merged microarray and RNAseq datasets with 656 and 252 samples, respectively. Interestingly, the four subtypes showed distinct clinical and biological features after comprehensive analyses of clinical features, multiomic profiles, immune infiltration, and drug sensitivity. S-I is basal/stem/mesenchymal-like and immune-excluded with marked transforming growth factor ß, epithelial-mesenchymal transition and hypoxia signals, increased sensitivity to olaparib, and intermediate prognosis. S-II is luminal/metabolism-active and responsive to androgen deprivation therapy with frequent TMPRSS2-ERG fusion and a good prognosis. S-III is characterized by moderate proliferative and metabolic activity, sensitivity to taxane-based chemotherapy, and intermediate prognosis. S-IV is highly proliferative with moderate EMT and stemness, frequent deletions of TP53, PTEN and RB, and the poorest prognosis; it is also immune-inflamed and sensitive to anti-PD-L1 therapy. Overall, based on miRNA-regulated gene profiles, this study identified four distinct PCa subtypes that could improve risk stratification at diagnosis and provide therapeutic guidance.

Systematic Chromatin Accessibility Analysis Based on Different Immunological Subtypes of Clear Cell Renal Cell Carcinoma.

BACKGROUND: Recent research of clear cell renal cell carcinoma (ccRCC) is focused on the tumor immune microenvironment (TIME). Chromatin accessibility is critical for regulation of gene expression. However, its role in different immunological subtypes of ccRCC based on immune cell infiltration has not been systematically studied. METHODS: Five hundred thirty patient data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) were adopted to estimate immune cell infiltration. Twenty-four types of immune cells were evaluated with single-sample Gene Set Enrichment Analysis (ssGSEA). Patients were divided into two clusters based on immune cell infiltration. Systematic chromatin accessibility analysis was conducted based on the two clusters. RESULTS: We compared the relative expression of the immune gene signatures among 530 patients of TCGA-KIRC using ssGSEA. Overall survival (OS) analysis revealed 10 types of immune cells were significantly associated with prognosis. Patients were divided into two clusters based on 24 types of immune cell infiltration. Immune cell signals as well as PD-1/PD-L1 signal were higher in cluster 1. Among the two clusters, 2,400 differential peaks were found in TCGA-KIRC Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) data. The distribution of differential peaks and prognosis-related immune cells in 23 chromosomes are essentially the same. There is no peak distribution downstream. The proportion of peaks upstream of the 5' transcription start site decreases, and both sides of binding regions of the TSS 0.1-1 kb becomes smaller. Enrichment analysis of GO and KEGG of these differential peaks showed that they are remarkably related to the immune regulation in tumor microenvironment. Known motifs and de novo motifs were found by linking motif annotations to different peaks. Survival analysis of related motif transcription factors were prognostic. The GSEA enrichment analysis showed that high SP1 expression positively correlates with TGF-beta signaling and inflammatory response, while negatively correlates with TNF-alpha signaling via NFKB. High KLF12 expression negatively correlates with interferon gamma response, IL2-STAT5 signaling, TNF-alpha signaling via NFKB, IL6-JAK-STAT3 signaling. CONCLUSION: The abnormality of chromatin accessibility may play an important regulatory role in ccRCC immunity.

MicroRNA-92a Inhibits the Cell Viability and Metastasis of Prostate Cancer by Targeting SOX4.

MicroRNAs (miRNAs) was confirmed to play an active role in the pathogenesis of prostate cancer (PCa). The expression and biological function for miR-92a in PCa remains unknown. In this study, we demonstrated that miR-92a expression was decreased in PCa tissues and cells lines. Overexpression miR-92a inhibited the cell viability, migration and invasion of PC-3 while inhibition of miR-92a led to opposite alteration of cell viability and metastasis of DU-145 cells. Mechanically, we confirmed that miR-92a interacted with 3'-UTR of SOX4 through the complementary sequences by luciferase reporter assay. qRT-PCR and western blot confirmed that miR-92a inhibited the expression of SOX4 in PCa cells. Moreover, overexpression of SOX4 reversed the inhibitory effects of miR-92a overexpression on PC-3 cell viability, migration and invasion, while knockdown of SOX4 suppressed the promoting effects of miR-92a knockdown on these biological functions of DU-145 cells. Therefore, our study indicates that miR-92a inhibits the growth and metastasis of prostate cancer by targeting SOX4, and can potentially serve as a biomarker and treatment target for PCa patients.

Revealing the prognostic landscape of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in metastatic castration-resistant prostate cancer patients treated with abiraterone or enzalutamide: a meta-analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), as markers of systematic inflammation response, have been reported to be indicators in metastatic castration-resistant prostate cancer (mCRPC), whereas their prognostic values remain conflict. This study was to assess the prognostic value of NLR and PLR in mCRPC patients and to assess the response of abiraterone or enzalutamide through using NLR and PLR. METHODS: Databases searching was conducted in the PubMed, EMBASE, Google Scholar, and the Cochrane Library for relevant published literature up to October 2019. Data extraction and quality evaluation were performed on the eligible studies. STATA 14.0 software was used to pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 3144 mCRPC patients were enrolled from 15 cohort studies in this meta-analysis. The pooled results demonstrated that elevated NLR had a significant association with inferior OS in mCRPC patients treated with abiraterone (HR = 1.63, 95% CI: 1.43-1.85, P < 0.001) and enzalutamide (HR = 1.48, 95% CI: 1.27-1.72, P < 0.001), whereas elevated NLR had no significant association with unfavorable PFS treated with abiraterone and enzalutamide, respectively. Elevated PLR had a significant association with an inferior OS (HR = 1.52, 95% CI: 1.16-1.98, P < 0.001) in mCRPC patients treated with abiraterone. CONCLUSIONS: NLR and PLR were effective biomarkers for predicting prognosis in mCRPC patients and served as indicators of the efficacy of personalized treatment of mCRPC using abiraterone or enzalutamide. Future, more randomized control trials (RCTs) are needed to investigate the promising value of hematologic parameters.

MiR-301a Promotes Cell Proliferation by Repressing PTEN in Renal Cell Carcinoma.

OBJECTIVE: Renal cell carcinoma (RCC) displays an increasing incidence and mortality rate worldwide in recent years. More and more evidence demonstrated microRNAs function as positive or negative regulatory factors in many cancers, while the role of miR-301a in RCC is still unclear. MATERIAL AND METHODS: The expression and clinical significance of miR-301a were assessed via bioinformatic software on open microarray datasets of the Cancer Genome Atlas (TCGA) and then confirmed by quantitative real-time PCR (qRT-PCR) in RCC cell lines. Loss of function assays were performed in RCC cell lines both in vitro and in vivo. Cell Counting Kit-8 (CCK-8), flow cytometry, luciferase reporter assays, Western blotting, and immunohistochemistry were employed to explore the mechanisms of the effect of miR-301a on RCC. RESULTS: By analyzing RCC clinical specimens and cell lines, we found a uniform increased miR-301a in expression in comparison with normal renal tissue or normal human proximal tubule epithelial cell line (HK-2). In addition, miR-301a upregulation correlated advanced stage and poor prognosis of clear cell RCC (ccRCC). Anti-miR-301a could inhibit growth and cell cycle G1/S transition in RCC cell lines. Moreover, we found that PTEN was identified as a direct target of miR-301a that might partially interrupt miR-301a-induced G1/S transition. Importantly, nude-mouse models revealed that knockdown of miR-301a delayed tumor growth. CONCLUSION: These results indicate that miR-301a functions as a tumor-promoting miRNA through regulating PTEN expression, representing a novel therapeutic target for RCC.

Prepubertal-type teratoma in a postpubertal patient: case report and review of literature.

Prepubertal-type teratomas are rare, especially in postpubertal patients. We present a case of a 43-year-old man with a palpable painless mass in the left-sided testis discovered by accident. Scrotal ultrasound and magnetic resonance imaging revealed a 2.7×2.0 cm mass inside the left testis, and malignancy could not be excluded, though classical serum tumor makers were within normal limits. Radical testicular resection was then conducted, and the pathologic report proved the mass to be a testicular epidermoid cyst, a rare form of prepubertal-type teratoma. Relevant published literature is also reviewed in our text.

Revealing Prognostic Value of Skeletal-Related Parameters in Metastatic Castration-Resistant Prostate Cancer on Overall Survival: A Systematic Review and Meta-Analysis of Randomized Controlled Trial.

BACKGROUND: The skeleton is a preferred site for prostate cancer metastasis, and once metastases occur, the disease becomes incurable. Increasing evidence indicates the prognostic value of skeletal-related parameters, but remains controversial. OBJECTIVE: To perform a systematic review of the existing literature on assessing the prognostic value of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BSAP), urinary N-telopeptide (uNTx), bone scan index (BSI), and Brief Pain Inventory Short Form (BPI-SF) score in castration-resistant prostate cancer (CRPC) patients with skeleton metastasis. EVIDENCE ACQUISITION: PubMed, Web of Science, Cochrane Library, Medline, OVID, and Embase between 2010 and 2019 were reviewed. Key terms included randomized trials, prostate cancer, alkaline phosphatase, bone-specific alkaline phosphatase, urinary N-telopeptide, bone scan index, and Brief Pain Inventory Short Form. Data were collected, checked, and analyzed from December 2019 to March 2020. Hazard ratios (HRs) and overall survival (OS) were extracted to estimate the relationship between the above parameters and OS in patients with metastatic prostate cancer (mPCa). EVIDENCE SYNTHESIS: A total of 1,055 studies were identified via initial screening, including 1,032 from database research and 23 from other sources. After deduplication, 164 records were further excluded according to titles and abstracts. The remaining 36 potential articles were carefully screened. In the end, 15 eligible studies syntheses, which were published between 2010 and 2019, comprised data for a total of 11,378 patients, whose mean age ranged from 66 to 72 years. The sample size ranged from 82 to 1,901 patients. And the median follow-up time ranged from 24 to 55 months. Based on 15 randomized controlled trials published between 2010 and 2019, higher ALP levels (HR = 1.60, 95% CI: 1.38-1.87 P < 0.001), higher BSAP levels (HR = 1.31, 95% CI: 1.11-1.54 P = 0.001), higher uNTx levels (HR = 1.40, 95% CI: 1.29-1.52 P < 0.001), BSI progression (HR = 1.18, 95% CI: 1.08-1.29 P < 0.001), and higher BPI-SF score (HR = 1.47, 95% CI: 1.35-1.61 P < 0.001) had an association with inferior OS. CONCLUSIONS: Higher levels of ALP/BSAP and uNTx, a higher BPI-SF score, and progression of BSI predict inferior OS in patients with mCRPC. More randomized control trials are needed to investigate the promising value of these parameters.