Expression of chemokine receptor CCR7 is a negative prognostic factor for patients with gastric cancer: a meta-analysis.

BACKGROUND: The prognostic significance of CC chemokine receptor type 7 (CCR7) for survival of patients with gastric cancer remains controversial. To investigate the impacts of CCR7 on clinicopathological findings and survival outcome in gastric cancer, we performed a meta-analysis. METHODS: A comprehensive search in PubMed, Embase, the Cochrane Library, and the CNKI database (1966 to November 2015) was undertaken for relevant studies. The relative risk and hazard ratios with their 95 % confidence intervals were used as measures to investigate the correlation between CCR7 expression and clinicopathological findings and overall survival rate. Sensitivity analysis was conducted to assess the stability of outcomes. RESULTS: Fifteen eligible studies comprising 1697 participants were included in our analysis. The pooled relative risks indicated CCR7 expression was significantly associated with deeper tumor invasion [0.61, 95 % confidence interval (CI) 0.45-0.84, p = 0.003], advanced stage (0.47, 95 % CI 0.32-0.69, p < 0.001), vascular invasion (2.12, 95 % CI 1.20-3.73, p = 0.009), lymph node metastasis (2.00, 95 % CI 1.48-2.70, p < 0.001), and lymphatic invasion (1.98, 95 % CI 1.43-2.72, p < 0.001) but not with age, tumor size, and histological type. The pooling of hazard ratios showed a significant relationship between positive CCR7 expression and worse 5-year overall survival rate (0.46, 95 % CI 0.31-0.70, p < 0.001). CONCLUSIONS: Our meta-analysis indicated high CCR7 expression is likely to be a negative clinicopathological prognostic factor for patients with gastric cancer and to predict a worse long-term survival outcome.

JMJD2A predicts prognosis and regulates cell growth in human gastric cancer.

A number of JmjC domain-containing histone demethylases have been identified and biochemically characterized in mammalian. JMJD2A is a transcriptional cofactor and enzyme that catalyzes demethylation of histone H3 lysines 9 and 36. Here in this study, we aim to explore the role of JMJD2A in human gastric cancer. Quantitative real-time PCR, Western blot and immunohistochemistry analyses reveal higher expression of JMJD2A in clinical gastric cancer tissues than that in normal gastric mucosa. JMJD2A expression is associated with tumor stage and nodal status, and high level of JMJD2A predicts poor overall and disease-free survival. Univariate and multivariate survival analyses demonstrate that JMJD2A could serve as an independent prognostic factor. Furthermore, we show that inhibition the expression of JMJD2A attenuates the growth and transformation of three lines of gastric cancer cells. Mechanically, JMJD2A knockdown induces apoptosis of gastric cancer cells by up-regulating the expression of pro-apoptotic proteins and by down-regulating anti-apoptotic protein. Finally, we show that JMJD2A level is correlated with the level of the pro-apoptotic microRNA miR-34a in gastric cancer tissues and JMJD2A represses the expression of miR-34a by decreasing its promoter activity. Those findings demonstrate that JMJD2A regulates gastric cancer growth and serves as an independent prognostic factor, and implicate that JMJD2A may be a promising target for intervention.

The RNA-binding protein PCBP2 facilitates gastric carcinoma growth by targeting miR-34a.

Gastric carcinoma is the fourth most common cancer worldwide, with a high rate of death and low 5-year survival rate. However, the mechanism underling gastric cancer is still not fully understood. Here in the present study, we identify the RNA-binding protein PCBP2 as an oncogenic protein in human gastric carcinoma. Our results show that PCBP2 is up-regulated in human gastric cancer tissues compared to adjacent normal tissues, and that high level of PCBP2 predicts poor overall and disease-free survival. Knockdown of PCBP2 in gastric cancer cells inhibits cell proliferation and colony formation in vitro, whereas opposing results are obtained when PCBP2 is overexpressed. Our in vivo subcutaneous xenograft results also show that PCBP2 can critically regulate gastric cancer cell growth. In addition, we find that PCBP2-depletion induces apoptosis in gastric cancer cells via up-regulating expression of pro-apoptotic proteins and down-regulating anti-apoptotic proteins. Mechanically, we identify that miR-34a as a target of PCBP2, and that miR-34a is critically essential for the function of PCBP2. In summary, PCBP2 promotes gastric carcinoma development by regulating the level of miR-34a.

Role of exhaled hydrogen sulfide in the diagnosis of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is often accompanied by increased excretion of hydrogen sulfide (H2S). This study aimed to explore the value of exhaled H2S in the diagnosis of CRC. METHODS: A total of 80 people with normal colonoscopy results and 57 patients with CRC were enrolled into the present observational cohort study. Exhaled oral and nasal H2S were detected by Nanocoulomb breath analyser. Results were compared between the two groups. Receiver operating characteristic (ROC) curves were analysed and area under the curves (AUCs) were calculated to assess the diagnostic value of exhaled H2S. Meanwhile, the clinicopathological features, including gender, lesion location and tumour staging of patients with CRC, were also collected and analysed. RESULTS: The amount of exhaled H2S from patients with CRC was significantly higher than that of those with normal colonoscopy results. The ROC curve showed an AUC value of 0.73 and 0.71 based on oral and nasal H2S detection, respectively. The exhaled H2S in patients with CRC was correlated with gender, lesion location and tumour progression, including depth of invasion, lymphatic metastasis and TNM (Tumor, Lymph Nodes, Metastasis) staging. CONCLUSION: Exhaled H2S analysis is a convenient and non-invasive detection method for diagnosing CRC, suggesting a potential role in population screening for CRC.

The value of metabolic LncRNAs in predicting prognosis and immunotherapy efficacy of gastric cancer.

Introduction: As a unique feature of malignant tumors, abnormal metabolism can regulate the immune microenvironment of tumors. However, the role of metabolic lncRNAs in predicting the prognosis and immunotherapy of gastric cancer (GC) has not been explored. Methods: We downloaded the metabolism-related genes from the GSEA website and identified the metabolic lncRNAs. Co-expression analysis and Lasso Cox regression analysis were utilized to construct the risk model. To value the reliability and sensitivity of the model, Kaplan-Meier analysis and receiver operating characteristic curves were applied. The immune checkpoints, immune cell infiltration and tumor mutation burden of low- and high-risk groups were compared. Tumor Immune Dysfunction and Exclusion (TIDE) score was conducted to evaluate the response of GC patients to immunotherapy. Results: Twenty-three metabolic lncRNAs related to the prognosis of GC were obtained. Three cluster patterns based on metabolic lncRNAs could distinguish GC patients with different overall survival time (OS) effectively (p<0.05). The risk score model established by seven metabolic lncRNAs was verified as an independent prognostic indicator for predicting the OS of GC. The AUC value of the risk model was higher than TNM staging. The high-risk patients were accompanied by significantly increased expression of immune checkpoint molecules (including PD-1, PD-L1 and CTLA4) and increased tumor tolerant immune cells, but significantly decreased tumor mutation burden (TMB). Consistently, TIDE values of low-risk patients were significantly lower than that of high-risk patients. Discussion: The metabolic lncRNAs risk model can reliably and independently predict the prognosis of GC. The feature that simultaneously map the immune status of tumor microenvironment and TMB gives risk model great potential to serve as an indicator of immunotherapy.

Up-regulated myeloid-derived suppressor cell contributes to hepatocellular carcinoma development by impairing dendritic cell function.

OBJECTIVE: Defective immune function is an important cause of tumor development. Accumulation of myeloid-derived suppressor cell (MDSC) associated with inhibition of dendritic cell (DC) function is one of the major immunological abnormalities in cancer. However, the molecular mechanism of the phenomenon remains unclear. MATERIAL AND METHODS: We evaluated T cell stimulatory activity and interleukin (IL)-12 production of DC in a mouse model of liver cancer (hepatocellular carcinoma [HCC] mice). Then we detected the frequency of MDSC in spleen, peripheral blood (PB), lymph node (LN) and tumor tissue of HCC mice and its potential mechanisms. We also evaluated IL-10 production of MDSC and mechanism by which MDSC inhibit DC function. RESULTS: Toll-like receptor (TLR)-ligand (LPS, CpG, poly(I:C))-induced IL-12 production of DC was decreased in HCC mice compared with control. The T cell stimulatory activity of DC was lower in HCC mice than in controls. Meanwhile, an increase in the frequency of MDSC in tumor development was detected in spleen, PB, LN and tumor, and the IL-10 levels were higher in HCC mice derived MDSC than in control. Furthermore, the MDSC inhibited TLR-ligand-induced IL-12 production of DC by IL-10 production and suppressed T cell stimulatory activity of DC. Finally, we demonstrated that the increase in the frequency of MDSC was mediated by MyD88-NF-kB pathway. CONCLUSIONS: Our study suggests a new role for MDSCs in HCC development by suppressing host immune responses, and these findings have important implications when designing immunotherapy protocols.

E2F1 Maintains Gastric Cancer Stemness Properties by Regulating Stemness-Associated Genes.

PURPOSE: To determine the regulatory role of E2F1 in maintaining gastric cancer stemness properties and the clinical significance of E2F1 in gastric cancer. MATERIALS AND METHODS: We conducted a tumor spheroid formation assay to enrich gastric cancer stem-like cells. The protein and mRNA expression levels of genes were measured using Western Blot and qRT-PCR. Lentivirus-mediated overexpression and downregulation of E2F1 were performed to evaluate the effect of E2F1 on the stemness properties of gastric cancer cells. The effect of E2F1 on gastric cancer cell sensitivity of 5-Fu was evaluated using cell viability assay and TdT-mediated dUTP Nick-End Labeling staining. We also analyzed the association between E2F1 expression and clinical characteristics in gastric cancer patients. The KM plotter database was used to analyze the relationship between E2F1 and overall survival in GC patients. RESULTS: We found that E2F1 expression was significantly higher in gastric cancer tissues than in the paired adjacent normal tissues (p < 0.05) and was positively correlated with tumor size (p < 0.05), T stage (p < 0.05), and differentiation degree (p < 0.05). KM plotter database demonstrated a close association between higher E2F1 expression level and worse overall survival of gastric cancer patients (p < 0.05). In vitro assay illustrated that E2F1 could regulate the expression of stemness-associated genes, such as BMI1, OCT4, Nanog, and CD44, and maintain the tumor spheroid formation ability of gastric cancer cells. E2F1 enhanced 5-Fu resistance in gastric cancer cells, and the E2F1 expression level was correlated with the prognosis of gastric cancer patients receiving 5-Fu therapy. The expression levels of stemness-associated genes were also significantly higher in gastric cancer tissues than the paired adjacent normal tissues (p < 0.05). A positive correlation was observed between E2F1 and BMI1 (r = 0.422, p < 0.05), CD44 (r = 0.634, p < 0.05), OCT4 (r = 0.456, p < 0.05), and Nanog (r = 0.337, p < 0.05) in gastric cancer tissues. The co-overexpression of E2F1 and stemness-associated genes was associated with worse overall survival. CONCLUSION: E2F1 plays a significant role in gastric cancer progression by maintaining gastric cancer stemness properties through the regulation of stemness-associated genes. The close association between E2F1 and poor prognosis of patients suggests that E2F1 could serve as a prognostic biomarker and a therapeutic target in gastric cancer patients.

Experimental data for computing semantic similarity between concepts using multiple inheritances in Wikipedia category graph.

This data article compiles the detailed and descriptive experimental data of Wikipedia-based semantic similarity approach called as Neighbourhood Aggregated Semantic Contribution (NASC), presented in Husain, et al. [1]. The JWPL (Java Wikipedia Library)-DataMachine and JWPL WikipediaAPI are used to extract the required Wikipedia features from Wikipedia dump. The dataset presents the disambiguated Wikipedia concepts of the gold standard word similarity benchmarks MC30 (English), RG65es (Spanish) and RG65fr (French) and their associated set of categories in the corresponding Wikipedia category graph (WCG). The dataset also contains the number of ancestors, common ancestors, pages, and common pages in the k-neighbourhood of the associated categories for different levels of parameter k in the English, Spanish, and French WCGs. The presented dataset can be used to assess the semantic similarity between Wikipedia concepts in English (MC30), Spanish (RG65es), and French (RG65fr) languages benchmarks. Moreover, the dataset will be useful for the further analysis and comparison of the taxonomic structures of the English, Spanish, and French WCGs.

LncRNA PVT1 induces aggressive vasculogenic mimicry formation through activating the STAT3/Slug axis and epithelial-to-mesenchymal transition in gastric cancer.

PURPOSE: Vasculogenic mimicry (VM), a vessel-like network formed by highly aggressive tumor cells, plays an important role in accelerating cancer progression. This special vascularization pattern is closely associated with a poor prognosis in various cancers. As yet, however, the regulatory mechanism of VM formation is largely unknown. In this study, we assess whether the long noncoding RNA PVT1 is involved in VM generation in gastric cancer. METHODS: VM formation was determined by immunohistochemistry using PAS/CD31 double staining in gastric cancers and Matrigel tube formation in vitro. qRT-PCR and Western blotting were used to assess mRNA and protein expression. Interaction between PVT1 and STAT3 was determined using a RNA pull-down assay. Luciferase reporter and chromatin immunoprecipitation assays were performed to evaluate transcriptional activity of STAT3 on the Slug gene promoter. RESULTS: We found that PVT1 can induce VM generation both in vitro and in vivo. Mechanistically, we found that PVT1 interacted with and activated STAT3 through a 850-1770 nt fragment. PVT1 facilitated STAT3 recruitment to the Slug promoter and transcriptionally enhanced Slug expression, thereby triggering epithelial-to-mesenchymal transition (EMT) and VM capillary formation. STAT3 inhibition effectively blocked PVT1-mediated VM. In primary gastric cancer samples, a positive correlation was found between PVT1 and Slug upregulation, and patients with a high PVT1 and Slug expression exhibited markedly shorter survival times. CONCLUSION: Our results shed light on the role of PVT1 in gastric cancer cell-dependent VM formation. Our findings provide valuable clues for the design of new anti-angiogenic therapeutic strategies. The PVT1/STAT3 axis may serve as a potential target in gastric cancer treatment.

LncRNA PVT1 Mediates Antiapoptosis and 5-Fluorouracil Resistance via Increasing Bcl2 Expression in Gastric Cancer.

PURPOSE: Plasmacytoma variant translocation 1 (PVT1) is a long noncoding RNA encoded by the human PVT1 gene, which has been verified to mediate tumorigenesis in gastric cancer. However, the underlying molecular mechanisms of PVT1 in gastric cancer (GC) remain largely unknown. METHODS: The tumorigenic ability of PVT1 was verified by subcutaneous and orthotopic mouse models. Flow cytometry assay and TdT-mediated dUTP Nick-End Labeling staining were conducted to explore the effects of PVT1 on gastric cancer cell apoptosis. We investigated the relative gene and protein that are involved in apoptosis in real-time PCR and western blot assay. The resistance to 5- Fluorouracil (5-Fu) caused by PVT1 was evaluated using cell viability assay. Then, to confirm the effects of PVT1 on 5-Fu resistance, we conducted the Kaplan-Meier analysis based on three public databases. RESULTS: We confirmed that PVT1 can promote the progression of gastric cancer. PVT1 inhibited the apoptosis of GC cells, which may account for its promotion on GC. We confirmed that PVT1 can regulate the expression of Bcl2 and enhance drug-resistance of gastric cancer to 5-Fu. Kaplan-Meier analysis showed that patients with high PVT1 expression do not experience survival related benefits from 5-Fu based chemotherapy; instead, therapy containing no 5-Fu chemotherapy can improve the first progression survival and overall survival of high PVT1 expression GC patients significantly. CONCLUSION: Our results showed that PVT1 can inhibit the apoptosis and enhance the 5-Fu resistance of gastric cancer through the activation of Bcl2. PVT1 has the potential to serve as an indicator to predict 5-Fu treatment resistance.

[Intralymphatic chemotherapy with adriamycin-adsorbing nanometric activated carbon:pharmacokinetic experiment with dogs].

OBJECTIVE: To observe the pharmacokinetics of adriamycin-adsorbing nanometric activated carbon in intralymphatic chemotherapy. METHODS: Two ml of suspension of activated carbon with the diameter of 21 nm was mixed with adriamycin 5 mg. Eighteen dogs were randomly divided into 6 equal groups. The above mentioned mixture was injected subserosally to the anterior wall of gastric antrum of the dogs. Thirty minutes, 1 h, 2 h, 1 day, and 3 days after the injection the gastroepiploic lymph nodes of the Groups 1 - 5 were obtained. And Group 6 underwent extraction of venous blood samples 5, 15, 30, 60, 120, and 240 minutes after the injection and extraction of thoracic duct fluid 5, 15, 30, 60, 120, 240, and 360 minutes after the injection. The adriamycin concentrations at different time points were determined by mass spectrometer. The lymphatic vessels and nodes at the gastric wall were observed by the naked eyes. RESULTS: Black tiny lymphatic vessels and lymph nodes were visualized around the injection areas immediately after the injection. Adriamycin content could be detected 30 min after the injection and lasted for 72 h at high levels with the peak content of (84.6 +/- 2.0) microg per gram tissue at 60 min in the perilymph node of gastroepiploic artery. The adriamycin concentration in the lymph fluid of thoracic duct reached the top level of 162.5 ng/ml 30 min after the injection, and then decreased slowly. Adriamycin could be still detected in lymph fluid 6 h after injection. No trace of adriamycin was found in the blood at any time points. CONCLUSION: The content of adriamycin can keep high and last long in the drainage of lymph node and lymph fluid in the treatment of intralymphatic chemotherapy using adriamycin-adsorbing nanometric activated carbon.

Gastric Cancer Stem Cells: Mechanisms and Therapeutic Approaches.

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. GC stem-like cells (GCSCs), with unlimited self-renewal, differentiation, and tumor-regenerating capacities, contribute significantly to the refractory features of GC and have gained increasing attention for their role in GC drug resistance, relapse, and metastasis. Therapies targeting GCSCs seem to be one of the most promising methods to improve the outcomes of GC patients. Extensive investigations have attempted to outline the regulatory mechanisms in GCSCs and to develop GCSCs-targeting therapies with which to diminish GC drug resistance, metastasis and relapse. To the best of our knowledge, there is a lack of reviews summarizing these studies. In this review, we systematically recapitulated findings regarding the regulatory mechanisms of GCSCs, as well as therapies that target GCSCs, hoping to support the development of prognostic biomarkers and GCSCs-targeting anticancer therapies in GC.

The Diverse Mechanisms of miRNAs and lncRNAs in the Maintenance of Liver Cancer Stem Cells.

Liver cancer is the second leading cause of cancer-related death worldwide. The high frequency of recurrence and metastasis is the main reason for poor prognosis. Liver cancer stem cells (CSCs) have unlimited self-renewal, differentiation, and tumor-regenerating capacities. The maintenance of CSCs may account for the refractory features of liver cancer. Despite extensive investigations, the underlying regulatory mechanisms of liver CSCs remain elusive. miRNA and lncRNA, two major classes of the ncRNA family, can exert important roles in various biological processes, and their diverse regulatory mechanisms in CSC maintenance have acquired increasing attention. However, to the best of our knowledge, there is a lack of reviews summarizing these findings. Therefore, we systematically recapitulated the latest studies on miRNAs and lncRNAs in sustaining liver CSCs. Moreover, we highlighted the potential clinical application of these dysregulated ncRNAs as novel diagnostic and prognostic biomarkers and therapeutic targets. This review not only sheds new light to fully understand liver CSCs but also provides valuable clues on targeting ncRNAs to block or eradicate CSCs in cancer treatment.

LncRNA PVT1 promotes angiogenesis via activating the STAT3/VEGFA axis in gastric cancer.

Angiogenesis can aggravate gastric cancer progression. LncRNAs exert important roles in regulating various cancer behaviors. However, the functions and mechanisms of lncRNAs in angiogenesis remain largely unknown. Here we demonstrated that lncRNA PVT1 was upregulated and significantly associated with high-microvessel density and poor prognosis in gastric cancer. Through gain- and loss-of PVT1 expression, we found PVT1 could obviously induce angiogenesis within tumors, in addition to promoting tumor growth in vitro and in vivo. Mechanistically, PVT1 directly interacted with the signal transducer activator phospho-STAT3 in the nucleus, and increased its protein stability by protecting it from poly-ubiquitination and proteasome-dependent degradation. The binding of PVT1 activated the STAT3 signalling pathway, and successively elevated VEGFA expression to stimulate angiogenesis. The positive correlation of PVT1 and VEGFA expression was also verified in gastric cancer specimens, and high levels of PVT1 and VEGFA in combination frequently predicted shorter survival time. Moreover, we revealed that PVT1 was a STAT3-responsive lncRNA, as STAT3 could occupy the PVT1 promoter to facilitate its transcription. The positive feed-back loop of PVT1 and STAT3 continuously enhanced the oncogenic effects. Collectively, our study first elucidates the mechanism of PVT1-mediated angiogenesis via evoking the STAT3/VEGFA signalling axis, which provides promising target for developing new therapeutic strategy in gastric cancer.

Sine Oculis Homeobox Homolog 1 Regulates Mitochondrial Apoptosis Pathway Via Caspase-7 In Gastric Cancer Cells.

Sine oculis homeobox homolog 1 (Six1) is crucial in normal organ development. Recently, Six1 is reported to display aberrant expression in various cancers and plays important roles in cancer development. However, the regulatory mechanism of Six1 in gastric cancer is largely unknown. In the current study, we found that Six1 was increased in gastric cancer tissues, and its upregulation significantly associated with lymph node metastasis (p=0.042) and poor differentiation (p=0.039). Next, we took advantage of public available microarray data to assess Six1 prognostic value with online K-M Plotter software in gastric cancer, which demonstrated that patients with higher Six1 expression had shorter survival time (p=0.02). To explore the underlying mechanism of Six1, we silenced its upregulation in gastric cells to detect cellular functions. Our results indicated that knock-down Six1 could decrease colony formation number and rendered cells sensitive to 5- Fluorouracil drug treatment. The flow cytometry analyses showed that Six1 silence could promote apoptosis but had little effect on cell cycle transition. Along this clue, we tested mitochondrial membrane potential with JC-1 assay, which suggested that Six1 inhibition could trigger mitochondrial apoptosis. Our subsequent results revealed that Six1 knock-down could reduce the level of anti-apoptotic protein Bcl-2, and caspase-7 but not caspase-3 was involved to execute the mitochondrial apoptosis pathway. Taken together, we find Six1 has oncogenic role in gastric cancer development, and silenced Six1 expression can promote mitochondrial apoptosis by repressing Bcl-2 and activating executor caspase-7. These findings suggest that Six1 may become a valuable prognostic and therapeutic target in gastric cancer.

Multifunctional gadolinium-labeled silica-coated Fe3O4 and CuInS2 nanoparticles as a platform for in vivo tri-modality magnetic resonance and fluorescence imaging.

The facile fabrication of Gd-labeled superparamagnetic Fe3O4 nanoparticles (NPs) and fluorescent CuInS2 (CIS) quantum dots conjugated with arginine-glycine-aspartic acid (RGD) peptides has been demonstrated, for tri-mode targeted T1-, T2-weighted magnetic resonance (MR) and fluorescence imaging of pancreatic cancer. The core-shell nanocomposites formed are water-dispersible, stable and biocompatible, as confirmed by MTT assay on BXPC-3 cells. Relaxivity measurements show a T1 relaxivity (r1) of 1.56 mM-1 s-1 and a T2 relaxivity (r2) of 23.22 mM-1 s-1, which enable T1- and T2-weighted MR imaging of cancer cells in vitro and in vivo. The MR imaging data clearly indicate that the multifunctional NPs can specifically target cancer cells with αvß3 integrin over-expression on the cell surface, through a receptor-mediated delivery pathway. The T1-weighted positive and T2-weighted negative enhancement in the MR imaging significantly improves the diagnosis accuracy, and fluorescence imaging of tumor tissue can assist in clinical surgery. These findings suggest that these multifunctional NPs could be used as a platform for bimodal imaging (both MR and fluorescence) in various biological systems.

Long non-coding RNA Linc00152 is involved in cell cycle arrest, apoptosis, epithelial to mesenchymal transition, cell migration and invasion in gastric cancer.

Gastric cancer remains a serious threat to public health with high incidence and mortality worldwide. Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play important roles in regulating gene expression and are involved in various pathological processes, including gastric cancer. To investigate the possible role of dysregulated lncRNAs in gastric cancer development, we performed lncRNA microarray and identified 3141 significantly differentially expressed lncRNAs in gastric cancer tissues. Next, some of deregulated lncRNAs were validated among about 60 paired gastric cancer specimens such as Linc00261, DKFZP434K028, RPL34-AS1, H19, HOTAIR and Linc00152. Our results found that the decline of DKFZP434K028 and RPL34-AS1, and the increased expression of Linc00152 positively correlated with larger tumor size. The high expression levels of HOTAIR were associated with lymphatic metastasis and poor differentiation. Since the biological roles of Linc00152 are largely unknown in gastric cancer pathogenesis, we assessed its functions by silencing its up-regulation in gastric cancer cells. We found that Linc00152 knockdown could inhibit cell proliferation and colony formation, promote cell cycle arrest at G1 phase, trigger late apoptosis, reduce the epithelial to mesenchymal transition (EMT) program, and suppress cell migration and invasion. Taken together, we delineate the gastric cancer lncRNA signature and demonstrate the oncogenic functions of Linc00152. These findings may have implications for developing lncRNA-based biomarkers for diagnosis and therapeutics for gastric cancer.

Long non-coding RNAs in gastric cancer: versatile mechanisms and potential for clinical translation.

Gastric cancer (GC) remains a serious threat to many people, representing the second leading cause of cancer-related death worldwide. The lack of early diagnostic biomarkers, effective prognostic indicators and therapeutic targets all account for the poor prognosis of GC. Therefore, the identification of novel molecular biomarkers for early diagnosis, therapeutic response, and prognosis are urgently needed. High-throughput sequencing has identified a large number of transcribed long non-coding RNAs (lncRNAs) throughout the human genome. Accumulating evidence demonstrates that these lncRNAs play multiple roles in regulating gene expression at the transcriptional, post-transcriptional, and epigenetic levels. Aberrant expression of lncRNAs occurs in various pathological processes, including GC. Many dysregulated lncRNAs in GC have been significantly associated with a larger tumor size, higher degree of tumor invasion, lymph node and distant metastasis, and poorer survival outcome. In this review, we will provide an overview of the pathogenesis of GC, the characteristics and regulatory functions of lncRNAs, and the versatile mechanisms of lncRNAs in GC development, as well as evaluate the translational potential of lncRNAs as novel diagnostic and prognostic biomarkers and therapeutic targets in GC.

lncRNA GAS5 enhances G1 cell cycle arrest via binding to YBX1 to regulate p21 expression in stomach cancer.

Long non-coding RNAs (lncRNAs), which have evolved as important gene expression modulators, are involved in human malignancies. The down-regulation of lncRNA growth arrest specific transcript 5 (GAS5) has been reported in several cancers, however, the underlying mechanism of lncRNA GAS5 in stomach cancer is poorly understood. In this study, we found that lncRNA GAS5 had lower expression in stomach cancer tissues than the normal counterparts. lncRNA GAS5 was shown to interact with Y-box binding protein 1 (YBX1), and lncRNA GAS5 knockdown was shown to accelerate YBX1 protein turnover without affecting YBX1 transcription. lncRNA GAS5 down-regulation reduced the YBX1 protein level, which decreased YBX1-transactivated p21 expression and abolished G1 phase cell cycle arrest in stomach cancer. These results delineate a novel mechanism of lncRNA GAS5 in suppressing stomach carcinogenesis, and the lncRNA GAS5/YBX1/p21 pathway we discovered may provide useful targets for developing lncRNA-based therapies for stomach cancer.

[Effect of injecting activated carbon ultramicroparticles around the gastric tumor on staining lymph node].

OBJECTIVE: To observe the effect of injecting activated carbon ultramicroparticles around the gastric tumor before or during operation on staining lymph nodes and guiding the lymphadenectomy of gastric cancer. METHODS: Forty-three cases of gastric cancer received activated carbon (AC) ultramicroparticles around the tumor by submucosal endoscopic injection 1 approximately 6 days before the operation and/or intraoperative subserosal injection (AC group), whereas 82 cases of gastric cancer without the injection were used as control group. The number of dissected lymph nodes, number of black-stained lymph nodes and its relation to the injection time, metastasis of lymph nodes, and the side effect of the procedure were analyzed. RESULTS: The average numbers of resected lymph nodes were 34 +/- 13 in the AC group, significantly higher than that in the control group (16 +/- 9, P < 0.05). The dissected N(2) lymph nodes in the AC group was 25 +/- 9, significantly higher than that in the control group (8 +/- 4, P < 0.05). The total ratio of black-stained lymph node was 60.3% in general, 71.3% for the N1 lymph nodes and 56.3% for the N(2) lymph nodes in the AC group. Satisfactory effect of black staining of lymph nodes could be seen 2 days after local gastric tissue injection of activated carbon ultramicroparticles. The metastasis rate was 67.4% in the AC group, not significantly different from that in the control group (63.4%, P > 0.05). In the patients of AC group the metastasis rate of black-stained lymph node was 26.8%, significantly higher than that of the unstained lymph nodes (3.3%) and higher than that of the control group (18.4%). No serious side effect happened after the activated carbon ultramicroparticles injection in local gastric tissue. CONCLUSION: Local injection of activated carbon ultramicroparticles around the tumor is an effective, easy and safe procedure to guide gastric cancer lymphadenectomy.