Up-regulation of miR-592 correlates with tumor progression and poor prognosis in patients with colorectal cancer

miR-592, as a potential biomarker, has been linked to several cancers. However, the expression level and prognostic value of miR-592 in CRC have not been elucidated. In this study, we detected the miR-592 expression in CRC serum, tumor tissues, adjacent non-tumor tissues (NATs) and four colorectal cancer cell lines by RT-PCR. Our data proved that miR-592 expression was up-regulated in clinical CRC serum and tissues (P < 0.05). Serum or tissue miR-592 in CRC metastatic patients also maintained a high level, compared to that in non-metastatic CRC patients (P < 0.05). After radical surgery, postoperative serum miR-592 level in CRC patients significantly decreased (P < 0.05). Our clinicopathological analysis revealed that high miR-592 was significant associated with the tumor size (P = 0.008), TNM stage (P = 0.026), distant metastasis (P = 0.004) and preoperative CEA level (P = 0.022), which led to a shorter overall survival rate in CRC patients (P = 0.032). Furthermore, we designed and transfected miR-592 mimics or inhibitors into the corresponding CRC lines, and our experiments in vitro demonstrated that miR-592 could promote cell proliferation, wound healing and invasion ability of CRC cells (P < 0.05), while miR-592 did not influence the CRC cell apoptosis (P > 0.05). All these results suggested that miR-592 functioned as a novel and potential carcinogen-initiated and metastasis-related biomarker in CRC, and down-regulation of miR-592 might be considered as a potentially significant molecular treatment strategy for CRC patients.     

Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial

BackgroundCytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS.MethodsThis study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1 g/day) or a matched placebo for a period of 8 weeks.ResultsOne hundred and seventeen subjects were assigned to either curcumin (n = 59) or placebo (n = 58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 following curcumin supplementation (p < 0.001). In the placebo group, serum levels of TGF-β were decreased (p = 0.003) but those of IL-6 (p = 0.735), TNF-α (p = 0.138) and MCP-1 (p = 0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 in the curcumin versus placebo group (p < 0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines.ConclusionResults of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.     

Decreased expression of microRNA-148a predicts poor prognosis in ovarian cancer and associates with tumor growth and metastasis

ObjectiveMicroRNA-148a (MiR-148a) had been reported to take part in some cancer progresses, but its clinical significance in ovarian cancer had been rarely reported. The purpose of this study was to evaluate the prognostic value of miR-148a as well as its roles in ovarian cancer progression.MethodsRelative expression of miR-148a in the plasma specimens of ovarian cancer patients was detected by qRT-PCR. Chi-square test was used to analyze the relationship between miR-148a expression and clinical characteristics. The overall survival was analyzed by Kaplan-Meier method and Cox regression analysis was used to evaluate the prognostic value of miR-148a. In addition, the ovarian cancer cell line SKOV-3 was separately transfected with pcDNA3-microRNA-148a over-expression vector and pcDNA3 empty vector to detect the functional roles of miR-148a in ovarian cancer progression.ResultsDecreased level of plasma miR-148a was observed in ovarian cancer patients compared with healthy controls. The expression level was associated with histopathologic grade, TNM stage and lymph node metastasis (P < 0.05 for all). Besides, patients with high level of miR-148a had a longer survival time than those with low level (40.3 months vs 31.6 months, log rank test, P = 0.002). Cox regression analysis indicated that miR-148a might be a potential biomarker for ovarian cancer prognosis (HR = 1.699, 95%CI = 1.175-2.456, P = 0.005). Moreover, cell experiments confirmed that miR-148a could inhibit proliferation, migration and invasion of ovarian cancer cells.ConclusionMiR-148a may be a potential prognostic factor for ovarian cancer and it can suppress tumor progression.     

Epidermal growth factor-like domain 7 promotes cell invasion and angiogenesis in pancreatic carcinoma

Epidermal growth factor-like domain 7 (EGFL7), also known as vascular endothelial stain, was firstly identified as a modulator of smooth muscle cell migration. Though the expression of EGFL7 was reported to be up-regulated during tumorigenesis, the clinical and biological functions of EGFL7 in pancreatic carcinoma (PC) were still not fully elucidated. In this study, we found that the serum EGFL7 level in PC tissues was statistically higher than that in normal subjects (p < 0.001), and its level in non-resectable patients was also higher than that in resectable ones (p = 0.013). Among these resectable PC patients, the postoperative EGFL7 expression was significantly down-regulated when tumors were resected (p = 0.018). Using the immunohistochemistry method, our results demonstrated that the positive expression of EGFL7 was significantly associated with the TNM stage (p = 0.024), lymph node metastasis (p = 0.003) and local invasion (p = 0.022), and the EGFL7 expression closely correlated to the micro-vessel density (MVD) in PC tissues by Spearman analysis (r = 0.941, p = 0.000). In vitro, EGFL7 was silenced by the small interference RNA in PC cells, and our data indicated that down-regulation of EGFL7 did not influence the cycle progression, proliferation, colony formation and apoptosis of PC cells (p > 0.05), whereas inhibition of EGFL7 expression could decrease PaCa-2 cell invasion (p < 0.05). More interestingly, by tubular formation, Chick embryo chorioallantoic membrane (CAM) and ELISA assays, our results revealed that silencing EGFL7 expression represented a strong inhibiting effect on tubular formation of micro-vessels through down-regulating the protein levels of VEGF and Ang-2 (p < 0.05). Our results raised the possibility of using EGFL7 as a potential prognostic biomarker and therapy target of PC, and down-regulation of EGFL7 might be considered to be a potentially important molecular treatment strategy for patients with PC.     

Expression of bcl-2 correlates with poor prognosis and modulates migration of nasopharyngeal carcinoma cells

BackgroundThe role of bcl-2 expression, bcl-2 inhibitor HA14-1, and matrix metalloproteinase (MMP)-2 is still unclear in nasopharyngeal carcinoma (NPC).MethodsFrom 1996 to 2000, 145 patients with newly diagnosed NPC who were treated with high dose radiotherapy were enrolled. The relationship between bcl-2 expression, TNM stage, and disease-specific survival was analyzed. Furthermore, the NPC cell line HONE-1 was used to confirm the relationship between bcl-2 and cell metastasis.ResultsAmong the 145 patients, 47 (32.4%) of them were bcl-2 positive. The expression of bcl-2 was significantly correlated with neck lymph node metastasis (p = 0.006), and patients with negative bcl-2 expression had better disease-free survival (p = 0.007). A Cox regression model revealed that only bcl-2 expression (p = 0.023) and stage IV (p = 0.043) were statistically significant in the prognosis of NPC. In vitro analysis also showed that treatment with the bcl-2 inhibitor HA14-1 exerted an inhibitory effect on migration and expression of MMP-2 in HONE-1 cells.ConclusionsBcl-2 expression represents an important and easily assayed prognostic factor, and it may play an important role in lymph node metastasis. Inhibition of the migration mediated by MMP-2 may be a key feature for the prevention of cancer metastasis.     

Effect of a high-intensity interval training on serum microRNA levels in women with breast cancer undergoing hormone therapy. A single-blind randomized trial

BackgroundThe role of microRNAs (miRs) in hormone therapy (HT) is of keen interest in developing biomarkers and treatments for individuals with breast cancer. Although miRs are often moderate regulators under homeostatic conditions, their function is changed more in response to physical activity.ObjectiveThis single-blind randomized trial aimed to explore the effect of high-intensity interval training (HIIT) on serum levels of miRs in individuals with early-stage breast cancer undergoing HT.MethodsHormone receptor-positive women with breast cancer and healthy women were randomly assigned to a healthy control group (n = 15), healthy group with HIIT (n = 15), breast cancer group with HT (HT, n = 26), and breast cancer group with HT and HIIT (HT + HIIT, n = 26). The exercise groups underwent interval uphill walking training on a treadmill 3 times a week for 12 weeks. At the end of the study, we analyzed changes in levels of cancer-related miRs (oncomiRs) and tumour suppressor miRs (TSmiRs) in response to the HT and HIIT.ResultsIn women with breast cancer versus healthy controls, the expression of some oncomiRs was significantly increased — miR-21 (P < 0.001), miR-155 (P = 0.001), miR-221 (P = 0.008), miR-27a (P < 0.001), and miR-10b (P = 0.007) — and that of some TSmiRs was significantly decreased — miR-206 (P = 0.048), miR-145 (P = 0.011), miR-143 (P = 0.008), miR-9 (P = 0.020), and let-7a (P = 0.005). Moreover, HT considerably downregulated oncomiRs and upregulated TSmiRs. HIIT for 12 weeks with HT significantly decreased the expression of the oncomiRs and significantly increased that of the TSmiRs as compared with HT alone.ConclusionsHITT could amplify the decrease and/or increase in expression of miRs associated with HT in women with breast cancer. A prospective trial could determine whether the use of circulating miRs for monitoring treatment can be useful in therapy decisions.Trial registrationIranian Registry of Clinical Trials (No.: IRCT201202289171N1).     

BSA-binding properties and anti-proliferative effects of amino acids functionalized polyoxomolybdates

Glycine decorated heteropolymolybdates, K₂Na[AsMo₆O₂₁(O₂CCH₂NH₃)₃]·6H₂O 1 and K₂Na₂[γ-Mo₈O₂₆(O₂CCH₂NH₃)₂]·6H₂O 2, have been synthesized and evaluated for in vitro anti-proliferative effects. The identity and high purity of compounds 1 and 2 were confirmed by elemental analysis, FT-IR spectrum, UV–vis spectrum, and X-ray diffraction. Crystal data for 2: triclinic, P-1, a = 9.792(2) Å, b = 10.077(2) Å, c = 10.351(2) Å, α = 83.865(4)°, β = 71.110(4)°, γ = 62.284(3)°, V = 854.3(3) Å³, Z = 1, R(final) = 0.0486. The inhibitory effects of 1 and 2 on human non-small cell lung cancer cell line A549 were investigated by MTT assay, nuclear staining, and the flow cytometry. It indicated that compound 1 inhibited the proliferation of A549 cells in a dose-dependent and time-dependent manner, which is more effective than the positive control, 5-fluorouracil (5-FU) (P < 0.05). The staining and flow cytometry results showed that compound 1 induced the apoptosis and necrosis of A549 cells and inhibit cell proliferation, which is associated with S-phase arrest. Compound 2 showed a modest activity in a dose-dependent manner. In addition, the interaction between compound 1 and bovine serum albumin (BSA) was evaluated by spectroscopic methods. The results showed that the compound 1 effectively quenched the intrinsic fluorescence of BSA via static quenching and changed the conformation of BSA.     

Effects of a Full-Body Massage on Pain Intensity,Anxiety, and Physiological Relaxation in Taiwanese Patients with Metastatic Bone Pain: A Pilot Study

Bone involvement, a hallmark of advanced cancer, results in intolerable pain, substantial morbidity, and impaired quality of life in 34%–45% of cancer patients. Despite the publication of 15 studies on massage therapy (MT) in cancer patients, little is known about the longitudinal effects of MT and safety in cancer patients with bone metastasis. The purpose of this study was to describe the feasibility of MT and to examine the effects of MT on present pain intensity (PPI), anxiety, and physiological relaxation over a 16- to 18-hour period in 30 Taiwanese cancer patients with bone metastases. A quasi-experimental, one-group, pretest-post-test design with repeated measures was used to examine the time effects of MT using single-item scales for pain (PPI-visual analog scale [VAS]) and anxiety (anxiety-VAS), the modified Short-Form McGill Pain Questionnaire (MSF-MPQ), heart rate (HR), and mean arterial pressure (MAP). MT was shown to have effective immediate [t(29) = 16.5, P = 0.000; t(29) = 8.9, P = 0.000], short-term (20–30 minutes) [t(29) = 9.3, P = 0.000; t(29) = 10.1, P = 0.000], intermediate (1–2.5 hours) [t(29) = 7.9, P = 0.000; t(29) = 8.9, P = 0.000], and long-term benefits (16–18 hours) [t(29) = 4.0, P = 0.000; t(29) = 5.7, P = 0.000] on PPI and anxiety. The most significant impact occurred 15 [F = 11.5(1,29), P < 0.002] or 20 [F = 20.4(1,29), P < 0.000] minutes after the intervention. There were no significant time effects in decreasing or increasing HR and MAP. No patient reported any adverse effects as a result of MT. Clinically, the time effects of MT can assist health care providers in implementing MT along with pharmacological treatment, thereby enhancing cancer pain management. Randomized clinical trials are needed to validate the effectiveness of MT in this cancer population.     

LATS2 as a poor prognostic marker regulates non-small cell lung cancer invasion by modulating MMPs expression

Large tumor suppressor 2 (LATS2) plays significant roles in tumorigenesis and cancer progression. This study was aimed to analyze the correlation between LATS2 expression and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). LATS2 expression was examined in 73 NSCLC clinical specimens and 22 normal lung tissues using immunohistochemistry. Low levels of LATS2 protein were inversely associated with the T classification (P = 0.001), N classification (P = 0.005) and clinical stage (P = 0.001) in NSCLC patients. Patients with lower LATS2 expression had a significantly shorter overall survival than patients with high LATS2 expression. Multivariate analysis suggested that low expression of LATS2 was an independent prognostic indicator (P = 0.002) for the survival of patients with NSCLC. Furthermore, overexpression of LATS2 resulted in mobility inhibition in NSCLC cell lines A549 and H1299, and reduced protein level of matrix metalloproteinase-2 (MMP-2) and MMP-9. On the contrary, LATS2 siRNA treatment enhanced cell mobility and increased MMP-2 and MMP-9 protein expression level. In conclusion, low expression of LATS2 is a potential unfavorable prognostic factor and promoted cell invasion and migration in NSCLC.     

MUC1 expression and its association with other aetiological factors and localization to mitochondria in preneoplastic and neoplastic gastric tissues

BackgroundThe molecular events that underlie the conversion of normal human gastric epithelium into adenocarcinoma are poorly understood. MUC1 overexpression and localization in mitochondria might confer cancer cells with attenuation of stress induced apoptosis. We studied MUC1 expression pattern, interaction with HSP70 and localization in mitochondria in preneoplastic and neoplastic human gastric tissues.MethodsImmunohistochemistry and Western blot were used to study MUC1 expression pattern and localization in mitochondria. Coimmunoprecipitation was used to study MUC1 interaction with HSP70. MUC1 expression was correlated with other causative features including erbB2 expression.ResultsMUC1 was expressed in 75.8% (147/194). MUC1 overexpression was detected in 50.0% (19/38 cases) dysplasia and 58.2% (32/55 cases) adenocarcinoma tissues. MUC1-CT–HSP70 interaction was seen in 71.66% (43/60 cases) and MUC1 localized to mitochondria in 33.33% (5/15) dysplasia samples and in 47.05% (8/17) adenocarcinoma samples. MUC1 expression showed significant association with smoking (χ² = 5.945; p < 0.015), alcohol consumption (χ² = 4.055; p < 0.044) and erbB2 positivity (χ² = 10.75; p < 0.001). MUC1 expression did not show appreciable association with age (χ² = 0.15; p < 0.698), sex (χ² = 0.22; p < 0.640) or Helicobacter pylori infection (χ² = 3.06; p < 0.080).ConclusionsSignificant correlation was found between MUC1 expression and smoking, alcohol and erbB2 expression. MUC1 showed aberrant expression in dysplasia and adenocarcinoma stages. MUC1 cytosolic tail was bound by HSP70 in all the stages but MUC1-CT was found to localize in mitochondria only in dysplasia and adenocarcinoma. MUC1-CT localization to mitochondria in dysplasia and adenocarcinoma might aid in the attenuation of epithelial stress response induced loss of polarity.     

HER2 codon 655 polymorphism is associated with advanced uterine cervical carcinoma

Objectives:It has been suggested that overexpression of HER2 in advanced cervical tumors can be considered an independent predictor of poor patient outcome.Design and methods:Employing PCR-RFLPs, we examined the distribution of HER2 Ile655Val (rs 1136201) genotypes and alleles in patients with advanced cervical cancer (n = 109) and controls (n = 220).Results:Odds ratio (OR) for patients with advanced cervical cancer with the HER2 Val/Val homozygous or Val/Ile heterozygous state was 1.778 (95% CI = 1.117–2.830, p = 0.0176). We also observed an association of the HER2 Val/Val genotype with advanced cervical cancer in the patient group OR = 3.706 (95% CI = 1.061–12.950, p = 0.0459). However, we did not find a significant association between the distribution of genotypes or alleles and cancer characteristics for the HER2 Ile655Val polymorphism.Conclusions:Our results indicate that the HER2 655Val variant may be associated with the incidence of advanced cervical cancer.     

Diagnostic and prognostic potentials of microRNA-27a in osteosarcoma

AimGrowing evidence suggest that the microRNA (miR)-23a/24-2/27a cluster may play a crucial role in mammary tumorigenesis and act as a novel class of oncogenes. Among these members, miR-27a has been reported to promote proliferation, migration and invasion in human osteosarcoma cells. The aim of this study was to detect the serum levels of miR-27a in osteosarcoma patients and to investigate its associations with clinicopathological features and prognosis.MethodsmiR-27a levels in sera from 166 osteosarcoma patients and 60 healthy controls were detected by real-time quantitative RT-PCR. Then, the associations of serum miR-27a level with clinicopathological factors or survival of osteosarcoma patients were further evaluated.ResultsCompared to healthy controls, the serum levels of miR-27a were significantly increased in osteosarcoma patients (P < 0.001). Importantly, miR-27a could efficiently screen osteosarcoma patients from healthy controls (Area under receiver operating characteristic curve, AUC = 0.867). Then, high miR-27a expression was more frequently occurred in osteosarcoma patients with advanced clinical stage (P = 0.001), positive distant metastasis (P = 0.01) and poor response to chemotherapy (P = 0.008). In Kaplan–Meier survival analysis, high miR-27a expression was a significant indicator for poor overall survival (P = 0.006) as well as poor disease-free survival (P = 0.01). Furthermore, multivariate analysis demonstrated that miR-27a expression was an independent and significant prognostic factor to predict overall survival (P = 0.01) and disease-free survival (P = 0.03).ConclusionmiR-27a expression may be elevated in sera of osteosarcoma patients and in turn contributes to aggressive progression of this malignancy. Detection of serum miR-27a levels may have clinical potentials as a non-invasive diagnostic/prognostic biomarker for osteosarcoma patients.     

Prognostic role of high Bmi-1 expression in Asian and Caucasian patients with solid tumors: A meta-analysis

Recently, many studies have shown that the B-cell-specific moloney leukemia virus insertion site 1 (Bmi-1) exhibits altered expression in various cancers and may serve as prognostic biomarkers. We performed a meta-analysis to evaluate the prognostic role of Bmi-1 expression in solid cancers. Studies were recruited by searching PubMed, Embase and the Cochrane Library. Thirty-nine articles including 40 studies were involved in this meta-analysis. Our results indicated that the Bmi-1 showed the opposite prognostic effect in Asian and Caucasian populations. High Bmi-1 expression as a negative predictor for overall survival (OS) in Asian patients (HR = 1.96, 95% CI 1.62–2.36), but a positive predictor in Caucasian populations (HR = 0.77, 95% CI 0.63–0.93). Furthermore, we took a further subgroup analysis based on tumor type in these two populations, respectively. In Asian cases, high expression of Bmi-1 was associated with poor OS in oesophageal carcinoma (HR = 1.93, 95% CI 1.52–2.46), gastric cancer (HR = 1.50, 95% CI 1.22–1.85), lung cancer (HR = 1.73, 95% CI 1.05–2.85), cervical cancer (HR = 2.80, 95% CI 2.26–3.47) and colorectal cancer (HR = 3.36, 95% CI 2.19–5.15), rather than in breast cancer and HCC. In Caucasian populations, high expression of Bmi-1 was associated with better OS in breast cancer (HR = 0.70, 95% CI 0.51–0.97), but it showed no significance in oesophageal carcinoma. In conclusion, high Bmi-1 expression was significantly associated with poor survival in Asian patients with oesophageal carcinoma, gastric cancer, lung cancer, colorectal cancer and cervical carcinoma, whereas high level of Bmi-1 can predict better prognosis in Caucasian patients with breast cancer.     

Consistent and Breakthrough Pain in Diverse Advanced Cancer Patients: A Longitudinal Examination

Although cancer pain, both consistent and breakthrough pain ([BTP]; pain flares interrupting well-controlled baseline pain), is common among cancer patients, its prevalence, characteristics, etiology, and impact on health-related quality of life (HRQOL) are poorly understood. This longitudinal study examined the experience and treatment of cancer-related pain over six months, including an evaluation of ethnic differences. Patients with Stage III or IV breast, prostate, colorectal, or lung cancer, or Stage II–IV multiple myeloma with BTP completed surveys on initial assessment and at three and six months. Each survey assessed consistent pain, BTP, depressed affect, active coping ability, and HRQOL. Among the respondents (n = 96), 70% were white, 66% were female, and had a mean age of 56 ± 10 years. Nonwhites reported significantly greater severity for consistent pain at its worst (P = 0.009), least (P ≤ 0.001), on average (P = 0.004), and upon initial assessment (P = 0.04), and greater severity for BTP at its worst (P = 0.03), least (P = 0.02), and at initial assessment (P = 0.008). Women also had higher levels of some BTP measures. Ethnic disparities persisted when data estimation techniques were used. Examined longitudinally, consistent pain on average and several BTP measures reduced over time, although not greatly, indicating the persistence of pain in the cancer experience. These data provide evidence for the significant toll of cancer pain, while demonstrating further health care disparities in the cancer pain experience.     

Functional glutathione peroxidase 3 polymorphisms associated with increased risk of Taiwanese patients with gastric cancer

BackgroundGlutathione peroxidase 3 (GPX3) can enhance an antioxidant's capacity and reduce genomic damage caused by oxidants and thus influence tumorigenesis. We investigated the role of GPX3 as a risk of gastric cancer.MethodsWe first conducted a case-control study to test for the association between 5 tagging single nucleotide polymorphisms (SNPs) of GPX3 and the risk of gastric cancer in Chinese. Multivariate logistic regression analysis was performed to estimate the genetic effect with adjustments for age and sex. Functional studies were performed by using the luciferase reporter assay to assess functional consequences of the significant SNPs.ResultsAmong five SNPs (rs3763013, rs8177412, rs3805435, rs3828599, and rs2070593) genotyped in 227 cases and 844 controls, 3 SNPs were significant: intronic SNP rs3805435 (OR = 0.70, P = 0.037), intronic SNP 3828599 (OR = 0.68, P = 0.025), and 3′ UTR SNP rs2070593 (OR = 0.48, P = 0.001). The two intronic SNPs rs3805435 and SNP rs3828599 were in linkage disequilibrium (D′ = 0.91).ConclusionsThe reporter assays showed significant difference in the luciferase expression between protective and risk alleles of 2o intronic SNPs (P = 0.004), whereas the 3′UTR SNP did not influence the luciferase expression. The intronic SNPs at GPX3 can influence gene expression leading to an alteration of gastric cancer risk.     

TMPRSS4 promotes invasiveness of human gastric cancer cells through activation of NF-κB/MMP-9 signaling

Transmembrane protease serine 4 (TMPRSS4) is a type-II transmembrane serine protease that is frequently upregulated in human cancers. However, little is known about the biological roles of TMPRSS4 in gastric cancer. In this study, we examined the effect of TMPRSS4 on gastric cancer cell proliferation, migration, and invasion. The expression and secretion of matrix metalloproteinase-9 (MMP-9) and activation of nuclear factor-κB (NF-κB) were determined. The involvement of NF-κB/MMP-9 signaling was checked. Our data showed that TMPRSS4 silencing significantly (P < 0.05) reduced the migration and invasion of AGS and MKN-45 gastric cancer cells, without affecting cell proliferation. Overexpression of TMPRSS4 significantly promoted cell migration and invasion. The expression and secretion of MMP-9 was significantly (P < 0.05) enhanced in TMPRSS4-overexpressing cells. TMPRSS4-overexpressing cells had a significantly (P < 0.05) lower level of IκBα and higher level of nuclear NF-κB. Luciferase reporter assay confirmed that overexpression of TMPRSS4 resulted in a 3–5-fold increase in NF-κB-dependent luciferase activity. Downregulation of MMP-9 significantly (P < 0.05) reversed the invasiveness of gastric cancer cells induced by TMPRSS4 overexpression. Moreover, pharmacological inhibition of NF-κB attenuated the invasion of TMPRSS4-overexpressing cells and the expression of MMP-9. Upregulation of TMPRSS4 enhances the invasiveness of gastric cancer cells, largely through activation of NF-κB and induction of MMP-9 expression. Our study provides the rationale for targeting TMPRSS4 in the treatment of gastric cancer.