N-terminal truncated carboxypeptidase E represses E-cadherin expression in lung cancer by stabilizing the Snail-HDAC complex.

The N-terminal truncated carboxypeptidase E (CPEΔN) protein, an alternative splicing product of the carboxypeptidase E gene, has recently been recognized as an independent predictor for the recurrence and metastasis of lung adenocarcinoma. In this study, we showed that CPEΔN may accelerate lung cancer invasion via an E-cadherin-dependent mechanism. In vitro experiments and in vivo bioluminescence imaging assay revealed CPEΔN promoted the mobility and invasion of human lung cancer cells by suppressing endogenous expression of E-cadherin, a critical regulator for epithelial tissue homeostasis. Further mechanistic analyses revealed that CPEΔN directly interacted with and stabilized the Snail/HDAC1/HDAC3 complex within the promoter region of the E-cadherin-encoding CDH1 gene. CPEΔN overexpression led to a reduction of histone H3K9 acetylation and an increase of H3K9 and H3K27 trimethylation in the CHD1 gene promoter and ultimately inhibited E-cadherin transcription. In addition, correlations among CPEΔN, E-cadherin expression and tumor progression in 195 cases of lung adenocarcinoma patients were analyzed. Higher nuclear expression of CPEΔN was detected in patients with advanced stage of lung adenocarcinoma. Nuclear expression of CPEΔN was negatively correlated with the cell membrane expression of E-cadherin. Collectively, our findings illustrated that CPEΔN was involved in the transcriptional regulation of the epithelial-mesenchymal transition-related gene CDH1 and provide novel insights into CPEΔN-associated lung cancer metastasis.

A Systematic Review of Comparing Single-incision Versus Traditional Laparoscopic Right Hemicolectomy For Right Colon Diseases.

BACKGROUND: Single-incision laparoscopic right hemicolectomy (SILS) has been promoted in clinic since 2008, but a systematic review of comparing SILS and traditional laparoscopic right hemicolectomy (TLS) with long-term follow-up is rare. Here, in this study, comparison of SILS and TLS with long-term follow-up was evaluated by a meta-analysis method. METHODS: All studies about SILS and TLS for right hemicolectomy from 2010 to 2018 were searched from databases including Medline, Embase, Cochrane Library, and Wanfang. Operation index, recovery, and midterm follow-up data were evaluated by fixed-effects models, random-effects models, and Begg test. RESULTS: We collected 22 studies with 2218 patients. SILS groups contained 1038 (46.7%) patients, and 1180 (53.3%) patients were observed in the TLS group. Patients' baseline data were similar in the 2 groups. Compared with TLS, SILS had shorter operation duration [standardized mean difference (SMD): -0.35, 95% confidence interval (CI): -0.61 to -0.08, P<0.001, χ=49.40], shorter hospitalization time (SMD: -0.27, 95% CI: -0.37 to -0.16, P<0.001, χ=9.17), slightly less blood loss (SMD: -0.23, 95% CI: -0.36 to -0.10; P<0.001; χ=5.36), and smaller incision length (SMD: -2.19, 95% CI: -3.66 to -0.71, P<0.001; χ=316.1). No statistical differences were observed in other figures. CONCLUSION: SILS is more convenient and has better efficacy than TLS and could provide a promising surgical approach for right colon diseases.

SET domain containing protein 5 (SETD5) enhances tumor cell invasion and is associated with a poor prognosis in non-small cell lung cancer patients.

BACKGROUND: SET domain containing 5 (SETD5) is related to the aggressiveness of prostate and mammary cancers, but its association with non-small cell lung cancer (NSCLC) is unknown. Therefore, the purpose of this research was to determine the expression pattern and function of SETD5 in NSCLC. METHODS: SETD5 was detected by immunohistochemical analysis in 147 patients with non-small cell lung cancer. SETD5 was overexpressed in A549 cells or suppressed with siRNA in H1299 cells. Wound healing and transwell assays were performed. The expression levels of SETD5, p-AKT/AKT, Snail, p-JNK/JNK, Slug, E-cadherin, Zo-1, p-P38/P38, occludin, α-catenin, p-ERK/ERK, and p-P90RSK/ P90RSK were assessed by western blot. RESULTS: Online analysis of overall survival in 1928 patients with NSCLC showed that the SETD5 gene was related to worse overall survival (OS)(P < 0.001). The positive expression rate of SETD5 in noncancerous tissues was lower than that in cancerous tissues (16.7% vs. 44.2%, P < 0.001). SETD5 was significantly correlated with advanced TNM stage (P < 0.001), lymph node metastasis (P < 0.001) and overall survival rate (P < 0.001). Overexpression of SETD5 in A549 cells increased migration and invasion, while deletion of SETD5 in H1299 cells decreased migration and invasion. After overexpression of SETD5, the expression of ZO-1 was downregulated, and that of Snail was upregulated. After overexpression of SETD5, the levels of p-ERK and its downstream factor p-p90rsk increased. CONCLUSION: These results suggest that SETD5 could regulate p-P90RSK and facilitate the migration and invasion of NSCLC and may be related to the poor prognosis of patients with NSCLC.

Improved blood compatibility of polyethersulfone membrane with a hydrophilic and anionic surface.

In this study, a novel triblock copolymer of poly (styrene-co-acrylic acid)-b-poly (vinyl pyrrolidone)-b-poly(styrene-co-acrylic acid) (P(St-co-AA)-b-PVP-b-P(St-co-AA)) is synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, and used for the modification of blood contacting surface of polyethersulfone (PES) membrane to improve blood compatibility. The synthesized block copolymer can be directly blended with PES to prepare PES membranes by a liquid-liquid phase separation technique. The compositions and structure of the PES membranes are characterized by thermogravimetric analysis (TGA), ATR-FTIR, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM); the surface charge density of the modified PES membrane was measured by Zeta-potential; the blood compatibility of the PES membranes was assessed by detecting bovine serum albumin (BSA) and bovine serum fibrinogen (BFG) adsorption, platelet adhesion, activated partial thromboplastin time (APTT), platelet activation, and thrombin-antithrombin III (TAT) generation. The results indicated that the blood compatibility of the modified PES membrane was improved due to the membrane surface modification by blending the amphiphilic block copolymer and the surface segregation of the block copolymer.