Increased expression of Psoriasin is correlated with poor prognosis of bladder transitional cell carcinoma by promoting invasion and proliferation.

Psoriasin, otherwise known as S100A7, is a member of the S100 protein family. With the key function of binding calcium, it is able to regulate a range of cellular functions. Altered Psoriasin expression is associated with poor clinical outcomes in several solid cancers. The present study aimed to examine the implication of Psoriasin in bladder cancer (BC). Expression of Psoriasin was examined in BC cell lines using PCR. Immunohistochemical (IHC) staining of Psoriasin was performed on a bladder disease spectrum tissue array. Plasmids were constructed to effectively knockdown and overexpress Psoriasin in BC cells and further utilized for in vitro BC cellular function assays. Association between Psoriasin expression and survival of patients with BC was evaluated using Kaplan­Meier survival analysis. Psoriasin was revealed to be expressed by both bladder epithelia and cancer cells as determined by IHC. Increased expression of Psoriasin was significantly correlated with a poor overall BC patient survival. Overexpression of Psoriasin in the EJ138 cell line increased cellular proliferation, adhesion and invasion, whereas knockdown exhibited the opposite effect on cellular functions in RT112 cells. Matrix metalloprotease (MMP)9 appeared to be the most affected of the three MMPs examined in these two BC cell lines. The analysis revealed a positive correlation in BC tumours between Psoriasin and MMP9. Overall, high Psoriasin expression was correlated with poor overall survival in BC patients and promoted invasiveness of BC cells via upregulation of MMPs. Psoriasin possesses certain prognostic and therapeutic potential in BC which requires further exploration.

Inhibition Of Glycogen Synthase Kinase 3 Beta Suppresses The Growth And Survival Of Skull Base Chordoma Cells By Downregulating Brachyury Expression.

PURPOSE: Chordomas are locally aggressive tumors arising from notochordal remnants. Brachyury, a protein coded by T-gene, is crucial for chordoma cell proliferation. The aim of this study was to evaluate the effects of glycogen synthase kinase 3 beta (GSK3ß) activity on brachyury expression and on the growth and survival of skull base chordoma cells. PATIENTS AND METHODS: In this study, 16 paraffin-embedded specimens of primary skull base chordomas were analyzed for the expression of phosphorylated GSK3ß and brachyury using immunohistochemistry. The UM-Chor1 cell line derived from a clival chordoma was treated with AR-A014418 (AR), an inhibitor of GSK3ß, and brachyury expression was analyzed by qRT-PCR and Western blotting. The possible mechanism by which brachyury regulates the Wnt/ß-catenin signaling pathway was investigated by immunocytochemistry. The effects of AR on cell proliferation as well as sensitivity to chemotherapeutic drugs were also examined. RESULTS: The results suggested that phosphorylated GSK3ß and brachyury were upregulated in chordoma tissues. The GSK3ß inhibitor (AR) decreased brachyury expression and suppressed the growth and survival of the chordoma cells, possibly via regulation of the Wnt/ß-catenin signaling pathway. Moreover, AR increased the sensitivity of chordoma cells to chemotherapeutic drugs in vitro. CONCLUSION: This study provides evidence for the clinical development of the GSK3ß inhibitor (AR-A014418) as a potential chemotherapeutic adjuvant for the treatment of chordoma.

Psoriasin overexpression confers drug resistance to cisplatin by activating ERK in gastric cancer.

Psoriasin, a member of the S100 multigenic family, which is aberrantly expressed in a variety of human tumors, is considered as an attractive molecular target for cancer treatment. The present study aimed to characterize the role of psoriasin in gastric cancer (GC), the associated pathways through which it contributes to cancer development and progression, and the effect of psoriasin on cellular response to pre-operative chemotherapy in patients with GC. Expression of psoriasin mRNA and protein were analyzed using quantitative polymerase chain reaction and immunohistochemistry of gastric cancer cohorts, respectively. Gastric cancer cell models with differential expression of psoriasin were generated using stable cell lines that overexpressed psoriasin. The in vitro biological functions of the cells in response to psoriasin overexpression and to chemotherapeutic agents were assessed using various cell-based assays. Psoriasin was overexpressed in patients with advanced GC, and high psoriasin levels led to poor clinical outcomes. Increasing psoriasin expression in GC cell lines promoted cell proliferation, migration and invasion in vitro. Furthermore, psoriasin overexpression caused alterations in the levels of epithelial-mesenchymal transition-associated proteins, and activated the extracellular signal-regulated kinase signaling pathway. Additionally, higher levels of psoriasin expression were significantly associated a lack of response to neoadjuvant chemotherapy in patients with GC. Psoriasin overexpression tended to decrease the sensitivity of GC cells to cisplatin, potentially by inhibiting apoptosis or increasing the S-phase population. Taken together, these results indicate that psoriasin may be a promising therapeutic target for GC treatment, and a potential molecular marker to predict patient response to pre-operative chemotherapy.

Tumor-originated exosomal lncUEGC1 as a circulating biomarker for early-stage gastric cancer.

Conventional tumor markers for non-invasive diagnosis of gastric cancer (GC) exhibit insufficient sensitivity and specificity to facilitate detection of early gastric cancer (EGC). We aimed to identify EGC-specific exosomal lncRNA biomarkers that are highly sensitive and stable for the non-invasive diagnosis of EGC. Hence, in the present study, exosomes from the plasma of five healthy individuals and ten stage I GC patients and from culture media of four human primary stomach epithelial cells and four gastric cancer cells (GCCs) were isolated. Exosomal RNA profiling was performed using RNA sequencing to identify EGC-specific exosomal lncRNAs. A total of 79 and 285 exosomal RNAs were expressed at significantly higher levels in stage I GC patients and GCCs, respectively, than that in normal controls. Through combinational analysis of the RNA sequencing results, we found two EGC-specific exosomal lncRNAs, lncUEGC1 and lncUEGC2, which were further confirmed to be remarkably up-regulated in exosomes derived from EGC patients and GCCs. Furthermore, stability testing demonstrates that almost all the plasma lncUEGC1 was encapsulated within exosomes and thus protected from RNase degradation. The diagnostic accuracy of exosomal lncUEGC1 was evaluated, and lncUEGC1 exhibited AUC values of 0.8760 and 0.8406 in discriminating EGC patients from healthy individuals and those with premalignant chronic atrophic gastritis, respectively, which was higher than the diagnostic accuracy of carcinoembryonic antigen. Consequently, exosomal lncUEGC1 may be promising in the development of highly sensitive, stable, and non-invasive biomarkers for EGC diagnosis.

Reduced Expression of RanBPM Is Associated with Poorer Survival from Lung Cancer and Increased Proliferation and Invasion of Lung Cancer Cells In Vitro.

BACKGROUND/AIM: Ran binding protein microtubule-organizing centre (RanBPM), also known as RanBP9, is a scaffold protein conserved through evolution. We investigated the role of RanBPM in human lung cancer. MATERIALS AND METHODS: Transcripts of RanBPM were determined in 56 human lung cancers along with paired normal lung tissues using real-time PCR. Association with prognosis was analyzed by online Kaplan-Meier survival analysis. In vitro lung cancer cell functional assays examined the impact of RanBPM-knockdown on cellular growth and invasion. RESULTS: Higher expression of RanBPM was observed in tumor when compared to paired normal lung tissues. Increased RanBPM expression was seen in patients with longer overall and disease-free survival. Knockdown of RanBPM in lung cancer cell lines resulted in increased growth and invasion in vitro. CONCLUSION: Increased expression of RanBPM associates with postponed disease progression and better prognosis. RanBPM plays an inhibitory role in regulating proliferation and invasion of lung cancer cells.

NHERF1 Suppresses Lung Cancer Cell Migration by Regulation of Epithelial-Mesenchymal Transition.

BACKGROUND/AIM: Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) has been reported to interact with many cancer-related proteins and plays an important role in cancer progression. However, little is known about the biological functions of NHERF1 in lung cancer cells. The aim of the current study was to explore whether NHERF1 is involved in transforming growth factor (TGF)-ß1-induced epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer cells. MATERIALS AND METHODS: The expression of NHERF1 and EMT-associated markers including E-cadherin, N-cadherin, snail family transcriptional repressor 1 (SNAI1) and snail family transcriptional repressor 2 (SLUG) were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and western blotting. The migratory properties of cells were assessed using a wound-healing assay. RESULTS: TGF-ß1-induced a pro-migratory response in the A549 lung cancer cell line, that was consistently associated with corresponding changes in the expression levels of EMT-related genes. The expression of NHERF1 significantly decreased in the TGF-ß1-induced A549 cells. Overexpression of NHERF1 significantly inhibited the migratory ability of cells and reversed the TGF-ß1-induced mesenchymal phenotype of A549 cells. CONCLUSION: These data showed an important role of NHERF1 in the EMT of non-small-cell lung cancer cells, as well as migration.