Clinical Significance and Underlying Mechanisms of CELSR3 in Metastatic Prostate Cancer Based on Immunohistochemistry, Data Mining, and In Silico Analysis.

Background: The treatment and survival rate of patients with metastatic prostate cancer (MPCa) remain unsatisfactory. Herein, the authors investigated the clinical value and potential mechanisms of cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) in MPCa to identify novel targets for clinical diagnosis and treatment. Materials and Methods: mRNA microarray and RNA-Seq (n = 1246 samples) data were utilized to estimate CELSR3 expression and to assess its differentiation ability in MPCa. Similar analyses were performed with miRNA-221-3p. Immunohistochemistry performed on clinical samples were used to evaluate the protein expression level of CELSR3 in MPCa. Based on CELSR3 differentially coexpressed genes (DCEGs), enrichment analysis was performed to investigate potential mechanisms of CELSR3 in MPCa. Results: The pooled standard mean difference (SMD) for CELSR3 was 0.80, demonstrating that CELSR3 expression was higher in MPCa than in localized prostate cancer (LPCa). CELSR3 showed moderate potential to distinguish MPCa from LPCa. CELSR3 protein expression was found to be markedly upregulated in MPCa than in LPCa tissues. The authors screened 894 CELSR3 DCEGs, which were notably enriched in the focal adhesion pathway. miRNA-221-3p showed a significantly negative correlation with CELSR3 in MPCa. Besides, miRNA-221-3p expression was downregulated in MPCa than in LPCa (SMD = -1.04), and miRNA-221-3p was moderately capable of distinguishing MPCa from LPCa. Conclusions: CELSR3 seems to play a pivotal role in MPCa by affecting the focal adhesion pathway and/or being targeted by miRNA-221-3p.

The biological function and clinical significance of STIL in osteosarcoma.

BACKGROUND: SCL/TAL1 interrupting locus (STIL) is associated with the progression of several tumors; however, the biological role of STIL in osteosarcoma remains poorly understood. METHODS: In this study, the clinical significance of STIL in osteosarcoma was analyzed by gene chip data recorded in public databases. STIL expression was silenced in osteosarcoma cell lines to observe the effects on proliferation, apoptosis, invasion, and migration. Differentially expressed genes (DEGs) in the osteosarcoma chip were analyzed using The Limma package, and STIL co-expressed genes were obtained via the Pearson correlation coefficient. The potential molecular mechanism of STIL in osteosarcoma was further explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. RESULTS: Osteosarcoma was associated with higher STIL expression compared to the control samples, and the standardized mean difference (SMD) was 1.52. STIL also had a good ability to distinguish osteosarcoma from non-osteosarcoma samples [area under the curve (AUC) = 0.96]. After silencing STIL, osteosarcoma cell proliferation decreased, apoptosis increased, and the migratory and invasion ability decreased. A total of 294 STIL differentially co-expressed genes were screened, and a bioinformatics analysis found that differentially co-expressed genes were primarily enriched in the cell signaling pathways. The protein-protein interaction (PPI) network indicated that the hub differentially co-expressed genes of STIL were CDK1, CCNB2, CDC20, CCNA2, BUB1, and AURKB. CONCLUSIONS: STIL is associated with osteosarcoma proliferation and invasion, and may be promote the progression of osteosarcoma by regulating the expression of CDK1, CCNB2, CDC20, CCNA2, BUB1 and AURKB.

Clinical significance and potential molecular mechanism of miRNA-222-3p in metastatic prostate cancer.

The clinical significance and underlying molecular mechanism of miRNA-222-3p in metastatic prostate cancer (MPCa) remain unclear. The present study used a large number of cases (n = 1,502) based on miRNA chip and miRNA sequencing datasets to evaluate the expression and diagnostic potential of miRNA-222-3p in MPCa. We applied a variety of meta-analytic methods, including forest maps, sensitivity analysis, subgroup analysis and summary receiver operating characteristic curves, to prove the final results. MiRNA-222-3p was reduced in MPCa and had a moderate diagnostic potential in MPCa. We screened 118 miRNA-222-3p targets using three different methods including miRNA-222-3p transfected MPCa cell lines, online prediction databases and differently upregulated genes in MPCa. Moreover, functional enrichment analysis performed to explore the potential molecular mechanism of miRNA-222-3p showed that the potential target genes of miRNA-222-3p were significantly enriched in the p53 signal pathway. In the protein-protein interaction network analysis, SNAP91 was identified as a hub gene that may be closely related to MPCa. Gene chip and RNA sequencing datasets containing 1,237 samples were used to determine the expression level and diagnostic potential of SNAP91 in MPCa. SNAP91 was found to be overexpressed in MPCa and had a moderate diagnostic potential in MPCa. In addition, miRNA-222-3p expression was negatively correlated with SNAP91 expression in MPCa (r = -0.636, P = 0.006). These results demonstrated that miRNA-222-3p might play an important role in MPCa by negatively regulating SNAP91 expression. Thus, miRNA-222-3p might be a potential biomarker and therapeutic target of MPCa.