Synthesis of a water-stable CsPbBr3 perovskite for selective detection of mercury ion in water.

By using the method of low-temperature crystallization, CsPbBr3 perovskite nanocrystals (PNCs) coated with trifluoroacetyl lysine (Tfa-Lys) and oleamine (Olam) were synthesized in aqueous solution. The structure of the CsPbBr3 PNCs was characterized by many methods, such as ultraviolet (UV)-visible absorption spectrophotometer, fluorescence spectrophotometer, transmission electron microscopy (TEM), and X-ray diffraction (XRD) pattern. The fluorescence emission of the CsPbBr3 PNCs is stable in water for about 1 day at room temperature. It was also found that the fluorescence of the PNCs could be obviously and selectively quenched after the addition of mercury ion (Hg2+ ), allowing a visual detection of Hg2+ by the naked eye under UV light illumination. The fluorescence quenching rate (I0 /I) has a good linear relationship with the addition of Hg2+ in the concentration range 0.075 to 1.5 mg/L, with a correlation coefficient (R2 ) of 0.997, and limit of detection of 0.046 mg/L. The fluorescence quenching mechanism of the PNCs was determined by the fluorescence lifetime and X-ray photoelectron spectroscopy (XPS) of the PNCs. Overall, the synthesis method for CsPbBr3 PNCs is simple and rapid, and the as-prepared PNCs are stable in water that could be conveniently used for selective detection of Hg2+ in the water environment.

Rapid Genotyping of Campylobacter coli Strains from Poultry Meat by PFGE, Sau-PCR, and fla-DGGE.

The genotyping of Campylobacter coli was done using three methods, pulsed-field gel electrophoresis (PFGE), Sau-polymerase chain reaction (Sau-PCR), and denaturing gradient gel electrophoresis assay of flagellin gene (fla-DGGE) and the characteristics of these assays were compared. The results showed that a total of 53 strains of C. coli were isolated from chicken and duck samples in three markets. All isolates were clustered into 31, 33, and 15 different patterns with Simpson's index of diversity (SID) values of 0.972, 0.974, and 0.919, respectively. Sau-PCR assay was simpler, more rapid, and had higher discriminatory power than PFGE assay. Fla-DGGE assay could detect and illustrate the number of contamination types of C. jejuni and C. coli without cultivation, which saved more time and cost than Sau-PCR and PFGE assays. Therefore, Sau-PCR and fla-DGGE assays are both rapid, economical, and easy to perform, which have the potential to be promising and accessible for primary laboratories in genotyping C. coli strains.

HDAC4 promotes the growth and metastasis of gastric cancer via autophagic degradation of MEKK3.

BACKGROUND: Histone deacetylases (HDACs) have been shown to be involved in tumorigenesis, but their precise role and molecular mechanisms in gastric cancer (GC) have not yet been fully elucidated. METHODS: Bioinformatics screening analysis, qRT-PCR, and immunohistochemistry (IHC) were used to identify the expression of HDAC4 in GC. In vitro and in vivo functional assays illustrated the biological function of HDAC4. RNA-seq, GSEA pathway analysis, and western blot revealed that HDAC4 activated p38 MAPK signalling. Immunofluorescence, western blot, and IHC verified the effect of HDAC4 on autophagy. ChIP and dual-luciferase reporter assays demonstrated that the transcriptional regulation mechanism of HDAC4 and ATG4B. RESULTS: HDAC4 is upregulated in GC and correlates with poor prognosis. In vitro and in vivo assays showed that HDAC4 contributes to the malignant phenotype of GC cells. HDAC4 inhibited the MEF2A-driven transcription of ATG4B and prevented MEKK3 from p62-dependent autophagic degradation, thus activating p38 MAPK signalling. Reciprocally, the downstream transcription factor USF1 enhanced HDAC4 expression by regulating HDAC4 promoter activity, forming a positive feedback loop and continuously stimulating HDAC4 expression and p38 MAPK signalling activation. CONCLUSION: HDAC4 plays an oncogenic role in GC, and HDAC4-based targeted therapy would represent a novel strategy for GC treatment.

DNMT1-induced miR-378a-3p silencing promotes angiogenesis via the NF-κB signaling pathway by targeting TRAF1 in hepatocellular carcinoma.

BACKGROUND: Angiogenesis plays an important role in the occurrence, development and metastasis of hepatocellular carcinoma (HCC). According to previous studies, miR-378a participates in tumorigenesis and tumor metastasis, but its exact role in HCC angiogenesis remains poorly understood. METHODS: qRT-PCR was used to investigate the expression of miR-378a-3p in HCC tissues and cell lines. The effects of miR-378a-3p on HCC in vitro and in vivo were examined by Cell Counting Kit-8 (CCK-8), Transwell, tube formation and Matrigel plug assays, RNA sequencing, bioinformatics, luciferase reporter, immunofluorescence and chromatin immunoprecipitation (ChIP) assays were used to detect the molecular mechanism by which miR-378a-3p inhibits angiogenesis. RESULTS: We confirmed that miR-378a-3p expression was significantly downregulated and associated with higher microvascular density (MVD) in HCC; miR-378a-3p downregulation indicated a short survival time in HCC patients. miR-378a-3p knockdown led to a significant increase in angiogenesis in vitro and in vivo. We found that miR-378a-3p directly targeted TNF receptor associated factor 1 (TRAF1) to attenuate NF-κB signaling, and then downregulated secreted vascular endothelial growth factor. DNA methyltransferase 1 (DNMT1)-mediated hypermethylation of miR-378a-3p was responsible for downregulating miR-378a-3p. Moreover, a series of investigations indicated that p65 initiated a positive feedback loop that could upregulate DNMT1 to promote hypermethylation of the miR-378a-3p promoter. CONCLUSION: Our study indicates a novel DNMT1/miR-378a-3p/TRAF1/NF-κB positive feedback loop in HCC cells, which may become a potential therapeutic target for HCC.

Expression of fatty acid-binding protein-4 in gastrointestinal stromal tumors and its significance for prognosis.

BACKGROUND: Fatty acid-binding proteins (FABPs) have been found to be involved in tumorigenesis and development. However, the role of FABP4, a member of the FABPs, in GISTs (Gastrointestinal stromal tumors) remains unclear. This study aimed to investigate the expression of FABP4 and its prognostic value in GISTs. METHODS: FABP4 expression in 125 patients with GISTs was evaluated by immunohistochemical analysis of tissue microarrays. The relationship between FABP4 expression and clinicopathological features and prognosis of GISTs was analyzed. RESULTS: Multiple logistic regression analysis showed that expression of FABP4 correlated with tumor size and mitotic index. Furthermore, FABP4 level, tumor size, mitotic index, and high AFIP-Miettinen risk were independent prognostic factors in GISTs. The Kaplan-Meier survival curve showed that the 5-year survival rate of patients with high-FABP4 expression GISTs was lower. CONCLUSIONS: These results suggested that high-FABP4 expression might be a marker of malignant phenotype of GISTs and poor prognosis.

Glutathione stabilized green-emission gold nanoclusters for selective detection of cobalt ion.

A glutathione stabilized Au nanoclusters (GSH-Au NCs) was synthesized here and used to selective detection of cobalt ion. The as-prepared GSH-Au NCs had strong green light emission around 500 nm, and the features of the NCs have been systematically characterized by UV-vis absorption, X-ray photoelectronic spectroscopic, Fourier transform infrared spectroscopy and transmission electron microscope characterization. The interactions between the GSH-Au NCs and metal ions was studied, and the results indicated that the fluorescence of the GSH-Au NCs could be quenched in the presence of Co2+ ion at pH of 6.0. The quenching ratio was linear with the concentration of Co2+ ions, and the calibration curve was I0/I = 0.1187cco + 0.6085 in the Co2+ concentration ranges from 2.0 to 50.0 µM with correlation coefficient (R2) of 0.9950 and the limit of detection (LOD, 3σ) of 0.124 µM. In addition, we collected environmental water samples to test the reliability of the method and demonstrated this method is simple, rapid, and selective.

LncRNA HOXA-AS3 promotes gastric cancer progression by regulating miR-29a-3p/LTßR and activating NF-κB signaling.

BACKGROUND: Gastric cancer (GC) is among the most common and deadliest cancers globally. Many long non-coding RNAs (lncRNAs) are key regulators of GC pathogenesis. This study aimed to define the role of HOXA-AS3 in this oncogenic context. METHODS: Levels of HOXA-AS3 expression in GC were quantified via qPCR. The effects of HOXA-AS3 knockdown on GC cells function were evaluated in vitro using colony formation assays, wound healing assays and transwell assays. Subcutaneous xenograft and tail vein injection tumor model systems were generated in nude mice to assess the effects of this lncRNA in vivo. The localization of HOXA-AS3 within cells was confirmed by subcellular fractionation, and predicted microRNA (miRNA) targets of this lncRNA and its ability to modulate downstream NF-κB signaling in GC cells were evaluated via luciferase-reporter assays, immunofluorescent staining, and western blotting. RESULTS: GC cells and tissues exhibited significant HOXA-AS3 upregulation (P < 0.05), and the levels of this lncRNA were found to be correlated with tumor size, lymph node status, invasion depth, and Helicobacter pylori infection status. Knocking down HOXA-AS3 disrupted GC cell proliferation, migration, and invasion in vitro and tumor metastasis in vivo. At a mechanistic level, we found that HOXA-AS3 was able to sequester miR-29a-3p, thereby regulating the expression of LTßR and modulating NF-κB signaling in GC. CONCLUSION: HOXA-AS3/miR-29a-3p/LTßR/NF-κB regulatory axis contributes to the progression of GC, thereby offering novel target for the prognosis and treatment of GC.

Decellularized gastric matrix as a mesh for gastric perforation repair.

The development of novel materials with effective defect-repairing properties will help avoid subtotal gastrectomy in patients with large gastric perforations. We prepared perfused decellularized gastric matrix (PDGM) and analyzed its components, spatial structure, biomechanics, cytotoxicity, and histocompatibility to validate its efficacy in the repair of gastric perforation. PDGM retained large amounts of gastric extracellular matrix, while residual glandular cells and muscle fibers were not found. The spatial structure of the tissue was well preserved, while the DNA and glycosaminoglycan contents were significantly decreased compared with normal gastric tissue (p < .01). There was no obvious deformation of the spatial structure and tissue elasticity of PDGM after sterilization by Cobalt-60 irradiation. The PDGM had good histocompatibility. PDGM was then used to repair a rat gastric perforation model. Radiography of the upper gastrointestinal tract at 24 hr postoperatively revealed no contrast agent leakage. There was evidence of early fibroblast proliferation, which was complicated by capillary regeneration. The hyperplastic gastric gland was slightly disarranged after repair. Defects of the muscular layer also healed a little with the regeneration process. PDGM is a nontoxic biocompatible biological mesh that may be useful for repairing relatively large gastric defects.

Clinical and prognostic significance of CC chemokine receptor type 8 protein expression in gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Surgical resection and tyrosine kinase inhibitors are defined as the main treatments but cannot cure patients with advanced GIST, which eventually develops into recurrence and acquired drug resistance. Therefore, it is necessary to identify prognostic biomarkers and new therapeutic targets for GISTs. CC chemokine receptor type 8 (CCR8) protein participates in regulation of immune responses. Recent studies on CCR8 in non-small cell lung cancer and colorectal cancer showed that it was highly expressed in tumor-infiltrating regulatory T cells and correlated with a poor prognosis. AIM: To detect CCR8 expression in GIST tissues and analyze its relationships with clinicopathological features and prognosis in patients with GISTs. METHODS: Tissue samples were used for the tissue microarrays construction. The microarrays were then subjected to immunohistochemical analyses to detect CCR8 expression. Next, Kaplan-Meier analysis was utilized to calculate the survival rate of patients with complete follow-up data, and the potential prognostic value of CCR8 was evaluated by Cox regression analysis. Finally, a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes single-gene enrichment chart of CCR8 was constructed using the STRING database. RESULTS: CCR8-positive signals were detected as brown or brown-yellow particles by immunohistochemistry located in the cytoplasm. Among 125 tissue samples, 74 had CCR8 high expression and 51 had low or negative expression. Statistical analyses suggested CCR8 was significantly correlated with tumor size, mitotic index, AFIP-Miettinen risk classification and tumor location. Kaplan-Meier and multivariate analyses showed that patients with low or negative CCR8 expression, mitotic index < 5/high-power fields (HPF) and tumor diameter < 5 cm had a better prognosis. Based on the STRING database, CCR8 was significantly enriched in biological processes such as tumor immunity, T lymphocyte chemotaxis, migration and pathways like the nuclear factor-κB and tumor necrosis factor pathways as well as intestinal immune regulation networks. CONCLUSION: CCR8 is a prognostic biomarker for malignant potential of GISTs, with high expression correlated with malignancy and poor prognosis.

Diagnostic and prognostic value of the peripheral natural killer cell levels in gastric cancer.

Peripheral blood lymphocyte subsets have been reported to be useful as prognostic and/or diagnostic markers for patients with cancer. However, the clinical value of peripheral blood lymphocyte subsets in gastric cancer (GC) has remained elusive. In the present study, peripheral CD3+, CD4+ and CD8+ T lymphocytes, B cells (CD19+), regulatory T cells (Tregs; CD4+CD25+CD127-) and natural killer (NK) cells (CD3-CDl6+CD56+) were detected by flow cytometry in 122 patients with GC, 80 healthy donors (HDs) and 80 patients with gastric ulcer (GU). NK cells (CD56+) were detected by immunohistochemical (IHC) analysis in 20 GC and three GU tissue samples. A receiver-operating characteristic (ROC) curve was used to determine the threshold of the peripheral NK cell level and survival analysis was performed to assess its prognostic value in patients with GC. The results indicated that the peripheral NK cell proportion in patients with GC (18.77%) was significantly higher than that in the HD (12.19%) and GU (12.74%) groups. IHC analysis suggested that the NK level in GC tumor samples was correlated with that in paired serum samples. ROC curve analysis indicated that the peripheral NK cell level (15.16%) was able to effectively identify patients with GC, a diagnostic sensitivity of 75.41% and a specificity of 77.45% were determined. Multivariate logistic regression analysis revealed that the peripheral NK cell level was independently associated with the T stage and survival analysis demonstrated that high levels of peripheral NK cells were associated with poor prognosis of patients with GC. In conclusion, the peripheral NK cell level may be a diagnostic and prognostic marker for patients with GC.

High expression of G protein subunit gamma 13 is associated with poor prognosis of gastrointestinal stromal tumor.

The G protein subunit gamma 13 (GNG13) plays an important role in olfaction, vision, and biological behavior. However, our knowledge of the relationship between GNG13 expression and the clinicopathological features of gastrointestinal tumors is insufficient. Therefore, we used the Oncomine database to evaluate the expression of GNG13 mRNA in gastric cancer, the result showed that there was no significant difference in the expression of GNG13 between gastric cancer and adjacent normal tissues, and GNG13 mRNA expression was assessed in 32 matched pairs of Gastrointestinal adenocarcinoma tissues and adjacent normal tissues as well as 32 matched pairs of gastrointestinal stromal tumor (GIST) and adjacent normal tissues by quantitative reverse transcription-polymerase chain reaction analysis. The results suggested that GNG13 is upregulated in gastrointestinal stromal tumors. Immunohistochemical analysis was used to detect the GNG13 in the tissues of 123 patients with GIST. High cytoplasmic expression of GNG13, which was observed in 65.85 % of GIST patients, significantly correlated with mitotic index(P = 0.036) and tumor size(P = 0.024). Multiple logistic regression analysis showed that the expression of GNG13 was significantly associated with tumor size. Kaplan-Meier analysis indicated that high GNG13 expression was associated with poor prognosis of GIST. Multivariate Cox regression analysis indicated that the expression of GNG13, mitotic index and tumor size were independent adverse prognostic factors of GIST. These findings suggest that GNG13 is associated with the malignant phenotype of GIST and may serve as a marker of poor prognosis.

BDH2 triggers ROS-induced cell death and autophagy by promoting Nrf2 ubiquitination in gastric cancer.

BACKGROUND: 3-Hydroxy butyrate dehydrogenase 2 (BDH2) is a short-chain dehydrogenase/reductase family member that plays a key role in the development and pathogenesis of human cancers. However, the role of BDH2 in gastric cancer (GC) remains largely unclear. Our study aimed to ascertain the regulatory mechanisms of BDH2 in GC, which could be used to develop new therapeutic strategies. METHODS: Western blotting, immunohistochemistry, and RT-PCR were used to investigate the expression of BDH2 in GC specimens and cell lines. Its correlation with the clinicopathological characteristics and prognosis of GC patients was analysed. Functional assays, such as CCK-8 and TUNEL assays, transmission electron microscopy, and an in vivo tumour growth assay, were performed to examine the proliferation, apoptosis, and autophagy of GC cells. Related molecular mechanisms were clarified by luciferase reporter, coimmunoprecipitation, and ubiquitination assays. RESULTS: BDH2 was markedly downregulated in GC tissues and cells, and the low expression of BDH2 was associated with poor survival of GC patients. Functionally, BDH2 overexpression significantly induced apoptosis and autophagy in vitro and in vivo. Mechanistically, BDH2 promoted Keap1 interaction with Nrf2 to increase the ubiquitination level of Nrf2. Ubiquitination/degradation of Nrf2 inhibited the activity of ARE to increase accumulation of reactive oxygen species (ROS), thereby inhibiting the phosphorylation levels of AktSer473 and mTORSer2448. CONCLUSIONS: Our study indicates that BDH2 is an important tumour suppressor in GC. BDH2 regulates intracellular ROS levels to mediate the PI3K/Akt/mTOR pathway through Keap1/Nrf2/ARE signalling, thereby inhibiting the growth of GC.

SNHG16/miR-605-3p/TRAF6/NF-κB feedback loop regulates hepatocellular carcinoma metastasis.

The mechanism by which miR-605-3p regulates hepatocellular carcinoma (HCC) metastasis has not been clarified. In this study, we found that miR-605-3p was down-regulated in HCC and that low miR-605-3p expression was associated with tumour thrombus and tumour satellites. HCC patients with low miR-605-3p expression showed shorter overall survival and disease-free survival after surgery. Overexpression of miR-605-3p inhibited epithelial-mesenchymal transition and metastasis of HCC through NF-κB signalling by directly inhibiting expression of TRAF6, while silencing of miR-605-3p had the opposite effect. We also found that SNHG16 directly bound to miR-605-3p as a competing endogenous RNA. Mechanistically, high expression of SNHG16 promoted binding to miR-605-3p and inhibited its activity, which led to up-regulation of TRAF6 and sustained activation of the NF-κB pathway, which in turn promoted epithelial-mesenchymal transition and metastasis of HCC. TRAF6 increased SNHG16 promoter activity by activating NF-κB, thereby promoting the transcriptional expression of SNHG16 and forming a positive feedback loop that aggravated HCC malignancy. Our findings reveal a mechanism for the sustained activation of the SNHG16/miR-605-3p/TRAF6/NF-κB feedback loop in HCC and provide a potential target for a new HCC treatment strategy.

DNA bioassays based on the fluorescence 'turn off' of silver nanocluster beacon.

Recognition and quantification of oligonucleotide sequences play important roles in medical diagnosis. In this study, a new fluorescent oligonucleotide-stabilized silver nanocluster beacon (NCB) probe was designed for sensitive detection of oligonucleotide sequence targets. This probe contained two tailored DNA strands. One strand was a signal probe strand containing a cytosine-rich strand template for fluorescent silver nanocluster (Ag NC) synthesis and a detection sections at each end. The other strand was a fluorescence enhancing strand containing a guanine-rich section for signal enhancement at one end and a linker section complementary to one end of the signal probe strand. After synthesis of the Ag NCs and hybridization of the two strands, the fluorescence intensity of the as-prepared silver NCB was enhanced 200-fold compared with the Ag NCs. Two NCBs were designed to detect two disease-related oligonucleotide sequences, and results indicated that the two target oligonucleotide sequences in the range 50.0-600.0 and 50.0-200.0 nM could be linearly detected with detection limits of 20 and 25 nM, respectively. The developed fluorescence method using NCBs for oligonucleotide sequence detection was sensitive, facile and had potential for use in bioanalysis and diagnosis.

Rapid synthesis of cesium lead halide perovskite nanocrystals by l-lysine assisted solid-phase reaction at room temperature.

Nowadays, there are many ways to obtain cesium lead halide perovskite nanocrystals. In addition to the synthesis methods carried out in solution, the solid-phase synthesis was reported involving grinding and milling. In this paper, we synthesized luminescent CsPbBr3/Cs4PbBr6 perovskite nanocrystals (PNCs) by three solid-phase synthesis methods (grinding, knocking, stirring) using l-lysine as a ligand. This is the first attempt to use an amino acid for assisting the solid phase synthesis of perovskite and to study the difference in the products obtained by the three solid phase synthesis methods. The results show that the productivity of the solid-phase synthesis methods can be greatly improved by adding l-lysine and the perovskites obtained by the methods are more resistant to water due to the addition of l-lysine. The simplicity of the synthesis process expanded the use of solid-phase synthesis to obtain more perovskites and provided potential applications of perovskite in analytical detection and sensing in aqueous solution.

Rafoxanide promotes apoptosis and autophagy of gastric cancer cells by suppressing PI3K /Akt/mTOR pathway.

Rafoxanide is commonly used as anti-helminthic medicine in veterinary medicine, a main compound of salicylanilide. Previous studies have reported that rafoxanide, as an inhibitor of BRAF V600E mutant protein, inhibits the growth of colorectal cancer, multiple myeloma, and skin cancer. However, its therapeutic effect on gastric cancer (GC) and the potential mechanism has not been investigated. Here, we have found that rafoxanide inhibited the proliferation of GC cells in vitro, arrested the cell cycle in the G0/G1 phase, and promoted apoptosis and autophagy in GC cells. Treatment with specific autophagy inhibitor 3-methyladenine drastically inhibited the apoptotic cell death effect by suppressing the switch from autophagy to apoptosis. Mechanistically, we found that rafoxanide inhibited the growth of GC cells in vitro by inhibiting the activity of the PI3K/Akt/mTOR signaling pathway. This process induced autophagy, which essentially resulted in the apoptosis of GC cells. Results from subcutaneous implanted tumor models in nude mice also indicated that rafoxanide inhibited the growth of GC cells in vivo. Taken together, our findings revealed that rafoxanide inhibited the growth of GC cells both in vitro and vivo, indicating a potential drug candidate for the treatment of GC.

HCCR-1 is a Novel Prognostic Indicator for Gastric Cancer and Promotes Cell Proliferation.

The role of the human cervical cancer oncogene (HCCR-1) in the development of various tumors has been elucidated; however, its expression and function in gastric cancer remains largely unknown. Accordingly, the expression of HCCR-1 and epidermal growth factor (EGF) were detected in paired gastric cancer tissues and cell lines by western blotting (WB) and immunohistochemistry (IHC). Furthermore, the correlations between HCCR-1 expression in 209 gastric cancer tissues and the clinicopathological features and disease prognosis were analyzed. A stable HCCR-1 overexpression cell line was established, and the influence of increased HCCR-1 expression on the growth of gastric cancer cells was observed in vivo and in vitro. The expression of HCCR-1 generally increased in gastric cancer tissues. Further, increased HCCR-1 expression in gastric cancer tissues was associated with tumor T stage and was an independent factor that influenced poor postoperative prognosis in gastric cancer patients. A positive correlation was also detected between the expression of EGF and HCCR-1 in a time- and dose-dependent manner. The overexpression of HCCR-1 might enhance the growth rate of gastric cancer cells in vitro, increase the number of colony forming units, and promote the growth, volume, and weight of subcutaneous tumors in nude mice. In conclusion, HCCR-1 is a gastric cancer oncogene, and its increased expression plays a critical role in the occurrence and development of gastric cancer. Hence, HCCR-1 could serve as a valuable marker for the postoperative prognostic assessment of gastric cancer patients.

HAX-1 promotes the migration and invasion of hepatocellular carcinoma cells through the induction of epithelial-mesenchymal transition via the NF-κB pathway.

The expression of HS-1-associated protein X-1 (HAX-1) plays a major role in the development of hepatocellular carcinoma (HCC). However, the function of HAX-1 in HCC metastasis is unclear. Quantitative real-time PCR and western blotting were used to examine HAX-1 expression in HCC cell lines with different metastatic potential, and in tumor tissues with or without intrahepatic metastasis. HCC tissue arrays (n = 144) were used to assess correlations between clinicopathological parameters and HAX-1 expression. We also examined the effect of HAX-1 on promoting HCC cell metastasis in vivo and in vitro. The results showed that the expression levels of HAX-1 were higher in metastatic HCC cell lines than in non-metastatic HCC cell lines. HAX-1 was also significantly upregulated in primary HCC tissues with intrahepatic metastasis compared with those without intrahepatic metastasis. HCC in patients with high HAX-1 expression is more likely to metastasize. HAX-1 expression was associated with malignant progression and poor prognosis, and HAX1 silencing inhibited HCC cell migration and invasion in vitro and decreased HCC cell lung metastasis in vivo, whereas HAX-1 overexpression had the inverse effect. Moreover, HAX-1 increased HCC cell metastasis by promoting the epithelial-mesenchymal transition (EMT) process. Finally, we revealed that HAX-1 modulated EMT in HCC cells by increasing NF-κB/p65 nuclear translocation. In conclusion, HAX-1 promotes HCC metastasis by EMT through activating the NF-κB pathway, suggesting that HAX-1 could be a potential therapeutic target for HCC treatment.

High-level expression of PRSS3 correlates with metastasis and poor prognosis in patients with gastric cancer.

BACKGROUND AND OBJECTIVES: Serine protease-3 (PRSS3) is a known contributor to the genesis and development of malignant tumors, although its role in gastric cancer (GC) is still unclear. METHODS: PRSS3 expression in GC tissue samples and its relationship with clinicopathological features were analyzed. Effects of GC cellular responses to the introduction of small interfering RNA (siRNA)-mediated and short hairpin RNA (shRNA)-mediated interference with tumor PRSS3 expression were also assessed. RESULTS: PRSS3 was significantly upregulated in GC tissues, and PRSS3 protein levels were higher in tumors that developed metastases soon after the surgery compared with those that remained metastasis-free. High expression of PRSS3 was associated with tumor N staging and independently predictive of postoperative prognosis in patients with GC. The V1 variant of PRSS3 was primarily detected in GC tissue and cell lines, the others (V2-V4) being scarcely detectable. Methylation and demethylation drugs had no impact on expression levels of any PRSS3 transcriptional variant. The downregulated PRSS3 expression suppressed GC cell growth, migration, and invasion in vitro and in vivo. CONCLUSIONS: PRSS3 appears to act as an oncogene of GC. High PRSS3 expression portends postoperative metastasis, serving as an effective biomarker of poor therapeutic outcomes.

Low expression of RASSF10 is associated with poor survival in patients with colorectal cancer.

The RASSF10 has been identified as a tumor suppressor in human colorectal cancer (CRC). However, the expression of RASSF10 in patients with CRC has not been evaluated for its potential use as a biomarker in the diagnosis and prognosis assessment of CRC. We analyzed the expression of RASSF10 mRNA (n=30) and protein (n=205) in CRC and matched noncancerous colon tissue samples to explore the relationships among RASSF10 expression, clinicopathological factors, and prognosis in patients with CRC. Our results showed that the expression of RASSF10 mRNA and protein in CRC-adjacent tissues was higher than that in CRC tissues. Low RASSF10 expression was associated with the T stage (P=.037, odds ratio, 0.664; 95% confidence interval, 0.452-0.975) and the N stage (P<.001, odds ratio, 0.318; 95% confidence interval, 0.184-0.549) of the tumors. In addition, univariate analysis revealed that patients with CRC with lower RASSF10 expression had poorer overall survival (OS; P<.001) and disease-free survival (DFS; P<.001). The 5-year OS and DFS rates were 48.2% and 28.3%, respectively, in patients with low RASSF10 expression and 82.2% and 62.6%, respectively, in patients with high RASSF10 expression. Multivariate Cox regression analysis revealed that the strongest predictors of OS and DFS were RASSF10 expression (P<.001 and P<.001, respectively), T stage (P=.003 and P=.009, respectively), and N stage (P=.005 and P=.026, respectively). These results demonstrate that low expression of RASSF10 in CRC tissues is significantly correlated with poor survival after curative resection and may serve as a useful biomarker predictive of CRC prognosis.