Netrin-1 promotes metastasis of gastric cancer by regulating YAP activity.

Yes-associated protein (YAP) is a major downstream molecular of the Hippo pathway, which plays important role in cancer development. Netrin-1 conveys oncogenic activity in many types of malignant tumors. However, the downstream signaling of netrin-1 mediating its oncogenic effects in gastric cancer (GC) is not well defined. Here, we aim to investigate the role of netrin-1 in metastasis potential of GC by regulating YAP. In this study, we showed that netrin-1 inhibition significantly decreased migration and invasion abilities of GC cells, while netrin-1 overexpression effectively reversed this effect. We also demonstrated that netrin-1 upregulated YAP expression via its transmembrane receptor neogenin. Furthermore, our in vitro and in vivo results showed that the effect of netrin-1 on GC cells migration and invasion abilities was regulated by YAP. Collectively, our results defined netrin-1 as a positive regulator of malignant tumor metastasis in GC by activating the YAP signaling, with potential implications for new approaches to GC therapy.

FOXC2 is up-regulated in pancreatic ductal adenocarcinoma and promotes the growth and migration of cancer cells.

The transcriptional factor Forkhead box protein C2 (FOXC2) was recently demonstrated to be up-regulated in various cancer types. However, its expression profile and the biological functions in pancreatic cancer remain unknown. In this study, we examined the expression pattern of FOXC2 in pancreatic ductal adenocarcinoma (PDAC) tissues and investigated the functions of FOXC2 in the progression of PDAC. It was found that the expression of FOXC2 was up-regulated in PDAC samples. Forced expression of FOXC2 promoted the growth and migration of the PDAC cells, while knocking down the expression of FOXC2 inhibited the growth and migration of the PDAC cells. Moreover, FOXC2 was found to interact with beta-catenin and promote cell growth by activating beta-catenin/TCF signaling. Taken together, this study demonstrated the oncogenic roles of FOXC2 in PDAC, and FOXC2 might be a therapeutic target for PDAC.

Secreted protein acidic and rich in cysteine enhances the chemosensitivity of pancreatic cancer cells to gemcitabine.

It has been previously shown that the simultaneous exposure of colon cancer cells MIP to irinotecan and secreted protein acidic and rich in cysteine (SPARC) enhances anticancer activity. However, whether there is same effect of SPARC in pancreatic cancer remains largely unknown. Therefore in this study, we aimed to investigate the role of SPARC played in the sensitivity of pancreatic cancer to gemcitabine. We first treated MIAPaCa2 and MIAPaCa2/SPARC69 cells with different concentrations of gemcitabine (2, 5, 10, and 20 µM) for 24, 48, and 72 h and selected the appropriated concentration for further study. Then we analyzed cell viability, cell cycle, and apoptosis and the levels of apoptosis-related proteins by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescence-activated cell sorting and Western blot were used, respectively. In this study, we found that gemcitabine inhibited the proliferation of pancreatic cancer cells in a time- and dose-dependent manner. Overexpression of SPARC increased the inhibiting effect of gemcitabine on pancreatic cancer cells. The colony size of MIAPaCa2/SPARC69 was much smaller than that of MIAPaCa2/V. There was a G0/G1 arrest with significant increase of apoptosis after gemcitabine treatment in MIAPaCa2/SPARC69 cells. Furthermore, our results demonstrated that overexpression of SPARC markedly increased the levels of pro-apoptotic proteins in gemcitabine-treated pancreatic cancer cells. The SPARC can enhance the chemosensitivity of pancreatic cancer cells to gemcitabine via regulating the expression of apoptosis-related proteins. These results have shown that the SPARC/ gemcitabine combination treatment may be a potentially useful therapeutic option for individuals diagnosed with pancreatic cancer.

Prolyl hydroxylase 3 inhibited the tumorigenecity of gastric cancer cells.

Gastric cancer is one of the most common malignancies and the second leading cause of cancer-related death in the world, and it is very urgent to develop novel therapeutic strategies. Although HIF-1α is the most highly characterized target of prolyl hydroxylase 3 (PHD3), PHD3 has been shown to regulate several signal pathways independent of HIF-1α. Here, we found that the expression of PHD3 was decreased in the clinical gastric cancer samples and reversely correlated with tumor size and tumor stage. Over-expression of PHD3 in the gastric cancer cells significantly inhibited cell growth in vitro and in vivo, while knockdown the expression of PHD3 promoted the tumorigenecity of gastric cancer cells. Mechanistically, it showed that PHD3 downregulated the expression of beta-catenin and inhibited beta-catenin/T-cell factor (TCF) signaling. Taken together, our findings demonstrate that PHD3 inhibits gastric cancer by suppressing the beta-catenin/TCF signaling and PHD3 might be an important therapeutic target in gastric cancer.

Optimizing postsurgical recovery for elderly patients with gastric cancer.

Based on a recent study by Li et al, this editorial examines the significance of enhanced recovery after surgery (ERAS) protocols for elderly patients with gastric cancer. Cancer-related mortality, which is overwhelmingly caused by gastric cancer, calls for effective treatment strategies. Despite advances in the field of oncology, conventional postoperative care often results in prolonged hospital stays and increased complications. The aim of ERAS is to expedite recovery, reduce surgical stress, and improve patient satisfaction. The study of Li et al showed that, compared to traditional care, ERAS significantly reduces mortality risk, shortens hospital stays, and decreases postoperative complications. These findings support the widespread implementation of ERAS protocols in surgical practice to enhance patient outcomes and healthcare value.

Targeting methyltransferase-like 5-mediated sphingomyelin metabolism: A novel therapeutic approach in gastric cancer.

Gastric cancer (GC) is a global health problem and a leading cause of cancer-related deaths, with its mortality rate ranking third among all cancers. The etiology and progression of GC are characterized by a complex interplay of genetic and epigenetic changes, which present challenges for its early diagnosis and effective treatment. Elucidating the mechanisms underlying the occurrence and development of GC and identifying novel biomarkers for early detection and prognosis are crucial to improving patient outcomes. This editorial examines the role of methyltransferase-like 5 (METTL5) in the progression of GC through sphingomyelin metabolism by considering an article published by Zhang et al in the World Journal of Gastrointestinal Oncology in 2024, which is entitled "METTL5 promotes GC progression via sphingomyelin metabolism". These authors investigated the biological behavior of METTL5 in GC by examining its expression patterns, clinical relevance, functional effect, and potential mechanisms, as well as its response to chemotherapy. This editorial provides valuable insights into the role of METTL5 in the progression of GC and its potential as a therapeutic target.

Retroperitoneal bronchogenic cyst: A case report and review of literature.

BACKGROUND: Bronchogenic cysts are rare developmental anomalies that belong to the category of congenital enterogenous cysts. They arise from lung buds and are present at birth. The embryonic foregut is their origin. Typically, they are located within the chest cavity, particularly in the cavum mediastinale of the thoracic cavity or lodged in the pulmonary parenchyma, and are considered a type of lung bud malformation. CASE SUMMARY: A 49-year-old male patient was admitted to the hospital due to the detection of a retroperitoneal mass during a physical examination. Two weeks before admission, the patient underwent a physical examination and routine laboratory tests, which revealed a space-occupying mass in the retroperitoneal region. The patient did not report any symptoms (such as abdominal pain, flatulence, nausea, vomiting, high fever, or chills). The computed tomography (CT) revealed a retroperitoneal space-occupying lesion with minimal enhancement and a CT value of approximately 36 Hounsfield units. The lesion was not delineated from the boundary of the pancreatic body and was closely related to the retroperitoneum locally. CONCLUSION: Following a series of tests, an abdominal mass was identified, prompting the implementation of a laparoscopic retroperitoneal mass excision procedure. During the investigation, an 8 cm × 7 cm cystic round-shaped mass with a distinct demarcation was identified in the upper posterior region of the pancreas. Subsequently, full resection of the mass was performed. Postoperative pathological examination reveled a cystic mass characterized by a smooth inner wall. The cystic mass was found to contain a white, viscous liquid within its capsule.

Long non-coding RNAs and pancreatic cancer: A multifaceted view.

Pancreatic cancer (PC) is a highly malignant disease with a 5-year survival rate of only 10%. Families with PC are at greater risk, as are type 2 diabetes, pancreatitis, and other factors. Insufficient early detection methods make this cancer have a poor prognosis. Additionally, the molecular mechanisms underlying PC development remain unclear. Increasing evidence suggests that long non-coding RNAs (lncRNAs) contribute to PC pathology,which may control gene expression by recruiting histone modification complexes to chromatin and interacting with proteins and RNAs. In recent studies, abnormal regulation of lncRNAs has been implicated in PC proliferation, metastasis, invasion, angiogenesis, apoptosis, and chemotherapy resistance suggesting potential clinical implications. The paper reviews the progress of lncRNA research in PC about diabetes mellitus, pancreatitis, cancer metastasis, tumor microenvironment regulation, and chemoresistance. Furthermore, lncRNAs may serve as potential therapeutic targets and biomarkers for PC diagnosis and prognosis. This will help improve PC patients' survival rate from a lncRNA perspective.

H19 encourages aerobic glycolysis and cell growth in gastric cancer cells through the axis of microRNA-19a-3p and phosphoglycerate kinase 1.

Numerous studies have been conducted on long non-coding RNAs (lncRNAs) in human tumors like gastric cancer (GC). Our research uncovers how aerobic glycolysis and cell proliferation in gastric cancer cells are related to H19. We discovered that H19 was highly expressed in tumor tissues and that patients with higher H19 expression have a poorer prognosis. Intriguingly, we applied the subcellular isolation, luciferase reporter, western blot analysis, MTT, colony formation experiments, and CDX Model in Mice to verify that H19 regulates aerobic glycolysis towards GC cell growth by H19/microRNA (miR)-19a-3p/phosphoglycerate kinase 1 (PGK1) axis. Together, our research offers proof that the H19/miR-19a-3p/PGK1 pathway aids in the regulation of aerobic glycolysis and cell proliferation in GC. This may offer an opportunity for novel therapeutic approaches to the treatment of GC.

Protective effect of clodronate-containing liposomes on intestinal mucosal injury in rats with severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) can result in intestinal mucosal injury. This study aimed to demonstrate the protective effect of clodronate-containing liposomes on intestinal mucosal injury in rats with SAP. METHODS: Liposomes containing clodronate or phosphate buffered saline (PBS) were prepared by the thin-film method. SAP models were prepared by a uniform injection of sodium taurocholate (2 mL/kg body weight) into the subcapsular space of the pancreas. Sprague-Dawley rats were randomly divided into a control group (C group), a SAP plus PBS-containing liposomes group (P group) and a SAP plus clodronate-containing liposomes group (T group). At 2 and 6 hours after the establishment of SAP models, 2 mL blood samples were taken from the superior mesenteric vein to measure the contents of serum TNF-alpha and IL-12. Pathological changes in the intestine and pancreas were observed using hematoxylin and eosin staining, while apoptosis was detected using TUNEL staining. In addition, the macrophage markers cluster of differentiation 68 (CD68) in the intestinal tissue was assessed with immunohistochemistry. RESULTS: At the two time points, the levels of TNF-alpha and IL-12 in the P group were higher than those in the C group (P<0.05). Compared with the P group, the levels of TNF-alpha and IL-12 decreased in the T group (P<0.05). The pathological scores of the intestinal mucosa and pancreas in the T group were lower than those of the P group. In the T group, large numbers of TUNEL-positive cells were observed, but none or few in the C and P groups. The number of CD68-positive macrophages decreased in the T group. CONCLUSIONS: Clodronate-containing liposomes have protective effects against intestinal mucosal injury in rats with SAP. The blockade of macrophages may provide a novel therapeutic strategy in SAP.

Identification of G-protein signaling modulator 2 as a diagnostic and prognostic biomarker of pancreatic adenocarcinoma: an exploration of its regulatory mechanisms.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) has a high rate of mortality. Unfortunately, it is difficult to diagnosis. This study aimed to develop a more in-depth understanding of the disease. METHODS: A total of 177 patients with PAAD were recruited from The Cancer Genome Atlas (TCGA) database. Microarray analysis was performed to identify differentially expressed genes (DEGs) in PAAD. The microarray data were adapted to the ingenuity pathway analysis (IPA) for annotation and visualization, followed by protein-protein interaction (PPI) network analysis. In vitro transwell migration assays were conducted to explore the molecular and functional characteristics of pancreatic adenocarcinoma cells (PANC-1) with stable low expression of G-protein signaling modulator 2 (GPSM2). Expression of GPSM2 and the associated hub genes were detected by reverse transcription-quantitative polymerase chain reaction (qPCR). RESULTS: The overexpression of GPSM2 was proved in PAAD, as compared with the healthy tissues, as well as its correlation with history of chronic pancreatitis, T stage, TNM stage and tumor grade. We described it as an independent prognostic factor and found that it could influence the infiltration of immune cells in the tumor microenvironment. Silencing of GPSM2 restrained the and migration of the cells. Microarray analysis identified 1,631 DEGs in PAAD cells. The PPI network analysis identified hub genes including CD44, ITGB1, ITGB5, ITGA2, ITGA5, AKT1, EGFR, NRAS and MAP2K1, and their relationship with GPSM2 was confirmed by qPCR. CONCLUSIONS: GPSM2 is a novel prognostic factor and therapeutic target for PAAD. GPSM2 promoted the migration of pancreatic adenocarcinoma cells .Targeting GPSM2 and its downstream genes may prolong the survival time of patients with PAAD.

Bioinformatic and experimental analyses of key biomarkers in pancreatic cancer.

The present study aimed to screen the key genes in pancreatic cancer and to explore the pathogenesis of pancreatic cancer. A total of three expression profiling datasets (GSE28735, GSE16515 and GSE15471) associated with pancreatic cancer were retrieved from the public gene chip database. The differentially expressed genes (DEGs) were screened by GEO2R and subjected to Gene Ontology (GO) and signaling pathway enrichment analysis. Furthermore, a protein interaction network was constructed. The GEPIA online database was used to screen for genes that affect the prognosis of pancreatic cancer. Finally, cell functional experiments were performed on the selected key genes. A total of 72 DEGs were identified, including 52 upregulated and 20 downregulated genes. Enrichment analysis revealed roles of the DEGs in endodermal cell differentiation, cell adhesion, extracellular matrix-receptor interaction and PI3K-Akt signaling pathway. In total, 10 key nodal genes were identified, including integrin subunit α 2 (ITGA2), ITGB6 and collagen α 1 chain 1. Through survival analysis, two genes with an impact on the prognosis of pancreatic cancer were identified, namely ITGA2 and ITGB6. Silencing of ITGB6 in a pancreatic cancer cell line significantly suppressed cell proliferation and induced cell cycle arrest at G2/M phase. The identified key genes and signaling pathways may help to deepen the understanding of the molecular mechanisms involved in pancreatic cancer and provide a theoretical basis to develop novel therapies.

MRI shows clodronate-liposomes attenuating liver injury in rats with severe acute pancreatitis.

BACKGROUND: Studies have revealed that macrophages play an important role in the development of severe acute pancreatitis (SAP). Activated macrophages can lead to a systemic inflammatory response, induce lipid peroxidation, impair membrane structure, result in injury to the liver and the other extrahepatic organs, and eventually result in multiple organ dysfunction syndrome by promoting excessive secretion of cytokines. Liver injury can further aggravate the systemic inflammatory response and increase mortality by affecting the metabolism of toxins and the release of excessive inflammatory mediators. Clodronate is a synthetic bisphosphonate, which is often used for treating bone changes caused by osteoporosis and other factors. In the current study, we created liposomes containing superparamagnetic iron oxide particles (SPIOs) for macrophage labeling and magnetic resonance imaging, using a novel method that can bind the clodronate to induce apoptosis and deplete macrophages. METHODS: Superparamagnetic Fe3O4 nanoparticles were prepared by chemical coprecipitation. SPIO-containing liposomes and SPIO-clodronate-containing liposomes were prepared by the thin film method. SAP models were prepared by injection of sodium taurocholate (2 ml/kg body weight) into the subcapsular space of the pancreas. Sprague-Dawley rats were randomly divided into a control group, a SAP plus SPIO-liposome group, and a SAP plus SPIO-clodronate-containing group. Two and six hours after SAP models were available, T2-weighted MRI scans (in the same plane) of the livers of rats in each group were performed. At the end of the scans, 2 ml of blood was taken from the superior mesenteric vein to measure the levels of serum amylase, ALT, AST, TNF-alpha, and IL-6. Pathological changes in the liver and pancreas were assessed. RESULTS: Transmission electron microscopy showed that the liposomes had a uniform size. No pathological changes in the pancreata of rats in the control group were noted. The pathological changes in the pancreata and livers of rats in the SAP plus SPIO-clodronate-containing liposome group were milder than those in the SAP plus SPIO-liposome group. The MRI signal intensity of the livers in the SAP plus SPIO-liposome and SAP plus SPIO-clodronate-containing groups was significantly lower than that in the control group. There were significant changes in the two experimental groups (P<0.01). In addition, the levels of serum amylase, ALT, AST, TNF-alpha, and IL-6 in rats in the SAP plus SPIO-liposome group were higher than those in the control group (P<0.01), while the corresponding levels in the SPIO-clodronate-containing liposome group were significantly lower than those in the SAP plus SPIO-liposome group (P<0.01). CONCLUSION: Clodronate-containing liposomes protect against liver injury in SAP rats, and SPIO can be used as a tracer for MRI examination following liver injury in SAP rats.

LncRNA SNHG15 Contributes to Immuno-Escape of Gastric Cancer Through Targeting miR141/PD-L1.

INTRODUCTION: Long non-coding RNAs (lncRNAs) have been demonstrated to participate in many biological processes and severs as important regulators during the progression of gastric cancer. METHODS: Here, we introduced human lncRNA SNHG15 which was highly expressed in gastric cancer and cells. Interestingly, the expression of SNHG15 was correlated with programmed cell death ligand 1 (PD-L1), which promotes the resistance of gastric cancer cells to immune responses. Meanwhile, SNHG15 downregulation suppressed the expression of PD-L1 and resistance of immune responses. RESULTS: Further, our results suggested that SNHG15 acted as a competing endogenous RNA (CeRNA) to sponge miR-141, which was downregulated in gastric cancers and negatively correlated to PD-L1. CONCLUSION: Our results suggested that SNHG15 improved the expression of PD-L1 by inhibiting miR-141, which in turn promoted the resistance of stomach cancer cells to the immune responses.

Expression profile of lncRNAs and mRNAs in intestinal macrophages.

Non-coding RNAs (ncRNAs) have been previously reported to serve an important role in transcription. In addition, several studies have revealed that long ncRNAs (lncRNAs) have a crucial role in human diseases. However, the association between lncRNAs and inflammation­induced intestinal macrophages in the intestinal mucosal barrier has remained elusive. In the present study, intestinal macrophages from healthy Sprague Dawley rats were divided into two groups: The experimental group, consisting of intestinal macrophages treated with 1 mg/l lipopolysaccharide (LPS) and the control group, composed of untreated cells. Differentially expressed (DE) lncRNAs and mRNAs between the control and experimental groups were identified using microarray profiling. The levels of DE mRNAs and lncRNAs were measured by reverse transcription­quantitative PCR (RT­qPCR). Furthermore, Gene Ontology (GO) and pathway enrichment analyses of DE mRNAs and lncRNAs were performed. To identify core regulatory factors among DE lncRNAs and mRNAs, a lncRNA­mRNA network was constructed. A total of 357 DE lncRNAs and 542 DE mRNAs between the LPS­treated and untreated groups were identified (fold-change >1.5; P<0.05). In addition, selected microarray data were confirmed by RT­qPCR. GO analysis of the DE mRNAs indicated that the biological functions of the upregulated mRNAs included inflammatory response, immune response, metabolic process and signal transduction, whereas those of the downregulated mRNAs were metabolic process, cell cycle, apoptosis and inflammatory response. In addition, pathway enrichment analysis of the upregulated mRNAs revealed that the most enriched pathways were the NF­κB signaling pathway, B­cell receptor signaling pathway and apoptosis, while the downregulated mRNAs were significantly involved in metabolic pathways, the phosphatidylinositol signaling system, cytokine­cytokine receptor interaction and the Toll­like receptor signaling pathway. The lncRNA­mRNA co­expression network suggested that lncRNAs NONMMUT024673 and NONMMUT062258 may have an important role in LPS­induced intestinal macrophages. The present study identified the DE profiles between LPS­ and non­LPS­treated intestinal macrophages. These DE lncRNAs and mRNAs may be used as potential targets for attenuating excessive inflammatory response in intestinal mucosal barrier dysfunction.

G-protein-signaling modulator 2 expression and role in a CD133+ pancreatic cancer stem cell subset.

BACKGROUND: To investigate the expression and role of G-protein-signaling modulator 2 (GPSM2) in a CD133+ pancreatic stem cell subset. MATERIALS AND METHODS: Pancreatic cancer stem cells (PCSCs) from the cell line PANC-1 were sorted into CD133+ and CD133- subsets by flow cytometry. The tumorigenic potential of the subsets was assessed by subcutaneous tumor formation experiments in nude mice. Differential expression of GPSM2 was examined by real-time quantitative-PCR (qPCR) and Western blotting. To silence GPSM2 expression, a shRNA lentiviral vector targeting GPSM2 was constructed and stably transfected into CD133+ PCSCs. The inhibitory efficiency of the GPSM2 gene was verified by qPCR and Western blotting. The proliferation, colony formation, and migration abilities of the transfected CD133+ pancreatic cancer cells were assessed by MTT, soft agar colony formation, and Transwell assays. RESULTS: CD133+ and CD133- cell subsets were successfully isolated from PANC-1 cells. The CD133+ subset subcutaneously formed tumors in nude mice that were significantly bigger (343.05±57.59 mm3 vs 176.86±32.58 mm3, P<0.01) and denser (4.13±0.37 g vs 1.07±0.21 g, P<0.01) than those of the CD133- group. The GPSM2 mRNA and protein expression was significantly higher in CD133+ cells than in CD133- cells. Stable downregulation of GPSM2 expression reduced the proliferation, colony formation, and migration abilities of CD133+ PANC-1 cells (P<0.05). CONCLUSION: The CD133+PANC-1 cells have obvious stem cell characteristics and increased GPSM2 expression. Downregulation of GPSM2 significantly reduces the proliferation and migration ability of the cells. Therefore, GPSM2 may provide an important target for regulating PCSCs.

[Corrigendum] Netrin­1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation.

During the preparation of the figures in the above article, the authors inadvertently selected images for the shCTL experiments portrayed in Fig. 5I and J (for the MGC803 and SGC7901 cell lines, respectively) that were generated from the same original data source. A corrected version of Fig. 5 is shown opposite, showing the correct data for the shCTL experiment performed in SGC7901 cells (Fig. 5J). This error did not affect the major conclusions reported in the paper. All the authors have agreed to this Corrigendum. The authors regret this error, and apologize for any confusion that it may have caused. [the original article was published in Oncol Rep 40: 2325­2333, 2018; DOI: 10.3892/or.2018.6614].

Netrin-1 promotes cell neural invasion in gastric cancer via its receptor neogenin.

Neural invasion (NI) is one of the important routes for local spread of gastric cancer (GC) correlated with poor prognosis. However, the exact cellular characteristics and molecular mechanisms of NI in GC are still unclear. Netrin-1(NTN1) as an axon guidance molecule was firstly found during neural system development. Importantly, NTN1 has an essential role in the progression of malignant tumor and specifically mediates the induction of invasion. In this study, we found NTN1 expression was significantly increased in 97 tumor tissues from GC patients and positively correlated with NI (p<0.05). In addition, we detected NTN1 knockdown significantly suppressed GC cells migration and invasion. Moreover, our results showed that reciprocity was observed between GC cells and neurites colonies in dorsal root ganglia (DRG)-GC cells co-culture vitro model. GC cells with NTN1 silencing could suppress their abilities to navigate along surrounding neuritis and this effect was depended on its receptor neogenin. In vivo, NTN1 inhibition also decreased GC cells sciatic nerve invasion. Taken together, our findings argue that NTN1 and its receptor neogenin might act synergistically in promoting GC cells neural invasion. Inhibiting the activity of NTN1 could be a potential strategy targeting NI in GC therapy.

MicroRNA-505 suppresses gastric cancer cell proliferation and invasion by directly targeting Polo-like kinase-1.

PURPOSE: The expression of microRNA-505 (miR-505) has been investigated in various cancers; however, its effect and mechanism in relation to gastric cancer (GC) are yet to be determined. Thus, the current evaluation aimed to examine the expression and potential role of miR-505 in GC. MATERIALS AND METHODS: Quantitative real-time PCR was carried out to analyze miR-505 expression in GC cells and tissues. We observed that miR-505 is differentially expressed in GC cells following transfection of its mimics or inhibitors. Changes in cell invasion, cell proliferation, and epithelial-mesenchymal transition markers were measured. RESULTS: These findings indicated that miR-505 expression is downregulated in both GC cell lines and GC tissues. In addition, knockdown miR-505 induced the invasion and proliferation of GC cells. Transfection of miR-505 mimics led to an elevation in N-cadherin expression but a decrease in E-cadherin expression. Furthermore, we have shown that miR-505 binds to the 3'-UTR region of Polo-like kinase-1. CONCLUSION: Our results indicated that miR-505 suppresses GC cell proliferation and invasion; it may be a valuable candidate gene for seeking therapy strategy for GC.