microRNA-145-5p inhibits prostate cancer bone metastatic by modulating the epithelial-mesenchymal transition.

Objective: To investigate the effects of miRNA-145-5p on the tumor development and progression of prostate cancer (Pca) bone metastasis. Methods: Levels of miRNA-145-5p were assessed by real-time quantitative PCR in PC3 (bone metastatic Pca cells), 22RV1 (non-metastatic Pca cells), RWPE-1 (non-cancerous prostate epithelial cells) and Pca tissues collected from patients with and without bone metastases. The impact of miRNA-145-5p on cell proliferation was tested by CCK8 assay, colony formation assay and flow cytometric cell cycle analysis. Effects on invasion and migration of PC3 cells were determined by Transwell and wound healing assays. Western blotting, enzyme-linked immunosorbent assay, and flow cytometry apoptosis analyses were also performed to assess roles in metastasis. Results: Levels of miRNA-145-5p were decreased in Pca bone metastases and miRNA-145-5p inhibited cell proliferation, migration and invasion. miRNA-145-5p inhibited the expression of basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF) and transforming growth factor-ß (TGF-ß) in PC3 cells. miR-145-5p increased the expression of the epithelial marker E-cadherin and reduced the expression of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9). It was found that miRNA-145-5p mediated the epithelial-mesenchymal transition (EMT) and induced apoptosis. Conclusions: miRNA-145-5p negatively regulated the EMT, inhibited Pca bone metastasis and promoted apoptosis in Pca bone metastasis. Mimicry of miRNA-145-5p action raises the possibility of a novel target for treating Pca with bone metastases.

Exosome-Derived miRNAs as Potential Biomarkers for Prostate Bone Metastasis.

Purpose: The purpose of this study was to identify the potential exosome-derived microRNAs (miRNAs) related to prostate cancer (Pca) bone metastasis. Methods: Two datasets were collected. One dataset was from the authors' institute, for which two groups of 10 patients each were designed: in the first one, the patients had early-stage localised Pca without bone metastasis, and in the other, the patients presented with Pca with bone metastasis. Then, the miRNA expression profiles of the blood exosomes were obtained and analysed. The other dataset was a public dataset of the miRNA expression transcriptome (GSE26964), which was downloaded from Gene Expression Omnibus (GEO). The results of both datasets were jointly analysed and the most bone-metastatic-related differentially expressed miRNAs (diff-miRNAs) were identified and further validated. Finally, a series of bioinformatics analyses were performed and the relationship between target genes of the diff-miRNAs and the pathogenesis and progression of bone metastasis of Pca were studied. Results: From the authors' dataset, in all, 313 diff-miRNAs were identified, of which 205 were up-regulated while 108 were down-regulated. From the GSE26964 dataset, 107 diff-miRNAs were found, of which 44 were up-regulated and 63 were down-regulated. Taking the intersection of the results of both datasets, four diff-miRNAs were identified: hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613. In all, 94 target genes of the four diff-miRNAs were predicted. After considering the intersection of the results from the GSE32269 dataset, we obtained 25 target genes. Although either positive or negative correlations were found among the diff-miRNAs with some of the target genes, there is a lack of evidence on how such correlations regulate the development and promotion of Pca bone metastasis. Conclusion: Hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613 are potential biomarkers for Pca bone metastasis.

An immune-related lncRNA model for predicting prognosis, immune landscape and chemotherapeutic response in bladder cancer.

Long noncoding RNAs (lncRNAs) participate in cancer immunity. We characterized the clinical significance of an immune-related lncRNA model and evaluated its association with immune infiltrations and chemosensitivity in bladder cancer. Transcriptome data of bladder cancer specimens were employed from The Cancer Genome Atlas. Dysregulated immune-related lncRNAs were screened via Pearson correlation and differential expression analyses, followed by recognition of lncRNA pairs. Then, a LASSO regression model was constructed, and receiver operator characteristic curves of one-, three- and five-year survival were established. Akaike information criterion (AIC) value of one-year survival was determined as the cutoff of high- and low-risk subgroups. The differences in survival, clinical features, immune cell infiltrations and chemosensitivity were compared between subgroups. Totally, 90 immune-related lncRNA pairs were identified, 15 of which were screened for constructing the prognostic model. The area under the curves of one-, three- and five-year survival were 0.806, 0.825 and 0.828, confirming the favorable predictive performance of this model. According to the AIC value, we clustered patients into high- and low-risk subgroups. High-risk score indicated unfavorable outcomes. The risk model was related to survival status, age, stage and TNM. Compared with conventional clinicopathological characteristics, the risk model displayed higher predictive efficacy and served as an independent predictor. Also, it could well characterize immune cell infiltration landscape and predict immune checkpoint expression and sensitivity to cisplatin and methotrexate. Collectively, the model conducted by paring immune-related lncRNAs regardless of expressions exhibits a favorable efficacy in predicting prognosis, immune landscape and chemotherapeutic response in bladder cancer.

The Expression and Potential Role of Tubulin Alpha 1b in Wilms' Tumor.

We explored the difference in expression of tubulin alpha 1b (TUBA1B) between Wilms' tumor (WT) and normal tissues (NT) from in-house patients and databases, to determine TUBA1B expression in WT and the predictive pathways of coexpressed genes. In-house RNA-sequencing data were performed with WT and NT from three patients from our institute. Other four RNA-sequencing and microarray data were also downloaded from multiple public databases. The TUBA1B expression between WT and NT was analyzed by Student's t-test and meta-analysis. The correlation between the expression of TUBA1B and other genes in each study was analyzed. Genes with p < 0.05 and r > 0.5 were considered as the coexpressing genes of TUBA1B. Overlapping the coexpressed genes of the five studies, including three in-house patients (3 WT vs. 3 NT), GTEx-TARGET (126 WT vs. 51 NT), GSE2172 (18 WT vs. 3 NT), GSE11024 (27 WT vs. 12 NT), and GSE73209 (32 WT vs. 6 NT), were performed with limma and VennDiagram packages in R software. The website of WEB-based GEne SeT AnaLysis toolkit were used to analyze the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations for the overlapped genes. The results showed that the relative expression of TUBA1B in WT tissues from in-house three patients was 280.0086, 141.7589, and 303.8292 and that in NT was 16.5836, 104.8141, and 12.79 (3 WT vs. 3 NT, p = 0.0285, ROC = 100%, SMD = 2.74). Student's t-test and meta-analysis in all studies revealed that the expression of TUBA1B was upregulated in WT tissues compared to that in NT (p < 0.05, SMD = 2.89, sROC = 0.98). Finally, the research identified the expression of TUBA1B in WT tissues was significantly upregulated than that in NT. The coexpressed genes of TUBA1B were enriched in the pathway of DNA replication, mismatch repair, cell cycle, pathogenic Escherichia coli infection, and spliceosome.

Nomogram for predicting overall survival in children with neuroblastoma based on SEER database.

PURPOSE: This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. METHODS: The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. RESULTS: In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients' age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. CONCLUSION: The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.

RNA-Sequencing, Connectivity Mapping, and Molecular Docking to Investigate Ligand-Protein Binding for Potential Drug Candidates for the Treatment of Wilms Tumor.

BACKGROUND Wilms tumor, or nephroblastoma, is a malignant pediatric embryonal renal tumor that has a poor prognosis. This study aimed to use bioinformatics data, RNA-sequencing, connectivity mapping, molecular docking, and ligand-protein binding to identify potential targets for drug therapy in Wilms tumor. MATERIAL AND METHODS Wilms tumor and non-tumor samples were obtained from high throughput gene expression databases, and differentially expressed genes (DEGs) were analyzed using the voom method in the limma package. The overlapping DEGs were obtained from the intersecting drug target genes using the Connectivity Map (CMap) database, and systemsDock was used for molecular docking. Gene databases were searched for gene expression profiles for complementary analysis, analysis of clinical significance, and prognosis analysis to refine the study. RESULTS From 177 cases of Wilms tumor, there were 648 upregulated genes and 342 down-regulated genes. Gene Ontology (GO) enrichment analysis showed that the identified DEGs that affected the cell cycle. After obtaining 21 candidate drugs, there were seven overlapping genes with 75 drug target genes and DEGs. Molecular docking results showed that relatively high scores were obtained when retinoic acid and the cyclin-dependent kinase inhibitor, alsterpaullone, were docked to the overlapping genes. There were significant standardized mean differences for three overlapping genes, CDK2, MAP4K4, and CRABP2. However, four upregulated overlapping genes, CDK2, MAP4K4, CRABP2, and SIRT1 had no prognostic significance. CONCLUSIONS RNA-sequencing, connectivity mapping, and molecular docking to investigate ligand-protein binding identified retinoic acid and alsterpaullone as potential drug candidates for the treatment of Wilms tumor.

A novel risk signature that combines 10 long noncoding RNAs to predict neuroblastoma prognosis.

Neuroblastoma (NBL) is the most frequently encountered extracranial solid neoplasm and impacts significantly on the survival of patients, especially in cases of advanced tumor stage or relapse. A long noncoding RNA (lncRNA) signature to predict the survival of patients with NBL is proposed in this paper. Differentially expressed lncRNA (DElncRNA) was selected using the Limma plus Voom package in R based on the RNA-sequencing data downloaded from the Therapeutically Applicable Research To Generate Effective Treatments database and Genotype-Tissue Expression database. Univariate cox regression analysis, least absolute shrinkage and selection operator regression analysis, and multivariate cox regression analysis were conducted to identify candidate DElncRNAs for the risk signature. Consequently, 10 DElncRNAs were designated as candidate DElncRNAs for the risk signature. Time-dependent receiver operating characteristic curves and Kapan-Meier survival curves confirmed the efficacy of the risk signature in predicting the survival of patients with NBL (area under the curve = 0.941; p ≤ .001). One of the DElncRNA constituent subparts (LINC01010) was significantly associated with the survival outcome of patients with NBL in GSE62564 (p = .004). Thus, a risk signature comprising 10 DElncRNAs was identified as effective for individual risk stratification and the survival prediction outcomes of patients with NBL.

Primitive neuroectodermal tumors of the abdominal wall and vulva in children: Report of two cases and review of the literature.

BACKGROUND: Primitive neuroectodermal tumors are rare, highly malignant small round cell tumors belonging to the Ewing sarcoma family. The purpose of this article is to present clinical manifestation, histology, treatment, and prognosis of two primitive neuroectodermal tumors (PNETs) in extremely rare anatomic locations, the abdominal wall and vulva. CASE SUMMARY: Case 1 was a 66-month-old girl with lesions on the abdominal wall; tumor size was about 3.4 cm × 6.1 cm × 2 cm. The patient underwent radical resection of the tumor. After the operation, an alternating vincristine, doxorubicin, and cyclophosphamide/ifosfamide and etoposide (IE) regimen was given for eight cycles, and the patient survived for 66 mo without progression. Case 2 was a 40-month-old girl, with a vulvar lesion; tumor size was about 3.3 cm × 5 cm × 2.5 cm. The tumor was partially resected by surgery. The family left treatment after two cycles of vincristine, pirarubicin, and cyclophosphamide/IE chemotherapy, and the patient died at home six months after surgery. CONCLUSION: PNET is a rare, fast-growing, highly malignant tumor that requires histologic and molecular analyses for exact diagnosis, and multimodal treatment is required to achieve a good prognosis.