Long non-coding RNA SNHG15 inhibits P15 and KLF2 expression to promote pancreatic cancer proliferation through EZH2-mediated H3K27me3.

Long non-coding RNA (lncRNA) is emerging as an critical regulator in multiple cancers, including pancreatic cancer (PC). Recently, lncRNA SNHG15 was found to be up-regulated in gastric cancer and hepatocellular carcinoma, exerting oncogenic effects. Nevertheless, the biological function and regulatory mechanism of SNHG15 remain unclear in pancreatic cancer (PC). In this study, we reported that SNHG15 expression was also upregulated in PC tissues, and its overexpression was remarkably associated with tumor size, tumor node metastasis (TNM) stage and lymph node metastasis in patients with PC. SNHG15 knockdown inhibited proliferative capacities and suppressed apoptotic rate of PC cells in vitro, and impaired in-vivo tumorigenicity. Additionally, RNA immunoprecipitation (RIP) assays showed that SNHG15 epigenetically repressed the P15 and Kruppel-like factor 2 (KLF2) expression via binding to enhancer of zeste homolog 2 (EZH2), and chromatin immunoprecipitation assays (CHIP) assays demonstrated that EZH2 was capable of binding to promoter regions of P15 and KLF2 to induce histone H3 lysine 27 trimethylation (H3K27me3). Furthermore, rescue experiments indicated that SNHG15 oncogenic function partially involved P15 and KLF2 repression. Consistently, an inverse correlation between the expression of SNHG15 and traget genes were found in PC tissues. Our results reported that SNHG15 could act as an oncogene in PC, revealing its potential value as a biomarker for early detection and individualized therapy.

14-3-3η is a novel growth-promoting and angiogenic factor in hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The continued search for novel therapeutic strategies for HCC is urgently required. In this study, we aimed to investigate the functions and clinical significance of 14-3-3η protein in HCC. METHODS: Expressions of genes and proteins were determined by quantitative reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry. Their functions were assessed by endothelial cell recruitment, tube formation, wound healing, flow cytometry, immunostaining, immunoprecipitation, and xenograft assay. A tissue microarray followed by univariate and multivariate analyses was performed to indicate the clinical significance. RESULTS: In HCC specimens, overexpression of 14-3-3η was observed not only in tumors but also in intratumoral vessels. In HCC and vascular endothelial cells, 14-3-3η stimulated proliferation and angiogenesis, but attenuated the functions of sorafenib. Briefly, 14-3-3η facilitated the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2). Then, by binding to the phosphorylated-ERK1/2 (p-ERK1/2), formed a functional positive feed-back loop. A xenograft model showed that, blockage of either 14-3-3η or ERK1/2 inhibited the tumor growth. Finally, tissue microarray analyses showed that overexpression of 14-3-3η, either in tumors or intratumoral vessels, contributed to the poor survival. CONCLUSIONS: The 14-3-3η-ERK1/2 feedback loop played a characteristic growth-promoting role in HCC, not only in tumors but also in intratumoral vessels. Further, 14-3-3η could be a potential therapeutic target for HCC and a biomarker for predicting sorafenib treatment response. LAY SUMMARY: Here we found that, 14-3-3η protein exhibited a characteristic growth-promoting effect in both tumor and intratumoral vessels of hepatocellular carcinoma by interacting with ERK1/2 signaling.

Meta-analysis of pylorus-preserving gastrectomy for middle-third early gastric cancer.

BACKGROUND: Pylorus-preserving gastrectomy (PPG) has been performed to reduce postprandial symptoms for some early gastric cancer (EGC) cases. The aim of this study was to evaluate the possible advantages after PPG for middle-third EGC in comparison with distal gastrectomy. MATERIALS AND METHODS: We searched Medline, Embase, and Science Citation Index Expanded for relevant studies. Statistical analyses were conducted to calculate the summary weighted mean differences (WMDs) and odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) using random-effects models. RESULTS: We identified 15 nonrandomized controlled trials (16 studies) with 1774 patients, which consisted of 11 studies for conventional PPG (CPPG) versus conventional distal gastrectomy (CDG) and 5 studies for laparoscopy-assisted PPG (LAPPG) versus laparoscopy-assisted distal gastrectomy (LADG). Meta-analysis of CPPG versus CDG revealed that CPPG had the advantage of prevention of early dumping syndrome (OR=0.18; 95% CI 0.12, 0.27), gastritis (OR=0.19; 95% CI 0.07, 0.53), duodenal juice reflux (OR=0.20; 95% CI 0.06, 0.66), and regaining of weight (WMD=3.53; 95% CI 2.34, 4.72). However, the incidence of gastric stasis was higher in the CPPG group than in the CDG group (OR=1.70; 95% CI 1.13, 2.57). Meta-analysis of LAPPG versus LADG revealed that LAPPG shortened the operation time (WMD=-21.12; 95% CI -31.33, -10.90) and did not increase the occurrence of postoperative complication (OR=0.72; 95% CI 0.41, 1.27). CONCLUSIONS: With the benefits of prevention of early dumping syndrome, duodenal juice reflux, gastritis, and regaining of weight, PPG can be an excellent option for middle-third EGC.

Inhibitory effect of biosynthetic nanoscale peptide Melittin on hepatocellular carcinoma, driven by survivin promoter.

Hepatic resection and orthotopic liver transplantation are the only potentially curative treatments for hepatocellular carcinoma (HCC) but are indicated only in a minority of patients. Biosynthetic nanoscale peptide Melittin (Mel) is postulated to disrupt microbial phospholipid membranes by formation of stable or transient pores. Survivin, a member of the inhibitor of apoptosis family, is transcriptionally upregulated in most malignant tissues but not in normal tissues. It has been reported that the survivin promoter activity is tumor-specific and makes it a good candidate for construction of gene therapy vectors. In the present study, a non-viral vector (pSURV-Mel), encoding Mel gene, was developed to evaluate its anti-tumor effect in HCC cell lines and in vivo in a mouse model of human HCC xenograft tumor. Our results showed that the survivin promoter is specifically activated in tumor cells, and the pSURV-Mel plasmid expressed Mel selectively in tumor cells and also induced cytotoxicity. Moreover, intratumoral Injection of pSURV-Mel significantly suppressed the growth of xenograft tumors. Mechanistically, pSURV-Mel induced cell death by an apoptosis-dependent pathway. All taken together, this study elucidates a relatively safe, highly effective and cancer specific gene therapy strategy for HCC. The mechanisms of non-viral vector-induced cell death which were revealed by this work will shed light on the construction of more powerful vectors for cancer therapy.