IntroductionThe aim of the study was to investigate the effect of CNRIP1 promoter methylation on the proliferative, invasive and migration potential of colorectal cancer cells, including its potential use for the early detection and prognostic assessment of colorectal cancer.Material and methodsQuantitative methylation-specific PCR (qMSP) was used to detect the methylation status of the CNRIP1 promoter region in peripheral blood samples drawn from patients with colorectal adenocarcinoma, benign colorectal adenoma, and matched healthy controls. Putative CpG methylation sites were then pyrosequenced. We subsequently suppressed CNRIP1 methylation within colon cancer cells via treatment with 5-azacytidine and overexpressed colon cancer cells by transfection with a CNRIP1-overexpression pcDNA3.0 plasmid. Thereafter, the CNRIP1 methylation status and mRNA and protein expressions levels were determined. Finally, the proliferative, invasive and migration abilities of cell lines were determined with the CCK-8 and Transwell cell assays.ResultsThere were differences in the methylation status at loci 2216, 2226, 2231, 2245, and 2254 within the promoter region of CNRIP1 between patients with colorectal adenocarcinoma, colorectal adenoma, and healthy volunteers. The methylation status of CpG sequence 2245 significantly correlated with tumor diameter, invasion depth, TNM stage, grade, and lymph node metastasis (p < 0.05). The proliferative, invasive and migration abilities of colon cancer cells treated with 5-azaC or transfected with a CNRIP1-overexpression plasmid were significantly impaired relative to negative controls (p < 0.05).ConclusionsThe methylation status at locus 2245 within the CNRIP1 promoter region has potential value for the early detection and prognostic evaluation of colorectal cancers. Demethylation of the CNRIP1 promoter or overexpression of CNRIP1 can reduce the proliferative and migration abilities of colon cancer cells.

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Polymersomes possess the self-assembly vesicular structure similar to liposomes. Although a variety of comparisons between polymersomes and liposomes in the aspects of physical properties, preparation and applications have been elaborated in many studies, few focus on their differences in drug encapsulation, delivery and release in vitro and in vivo. In the present work, we have provided a modified direct hydration method to encapsulate anti-cancer drug paclitaxel (PTX) into PEG- b -PCL constituted polymersomes (PTX@PS). In addition to advantages including narrow particle size distribution, high colloid stability and moderate drug-loading efficiency, we find that the loaded drug aggregate in small clusters and reside through the polymersome membrane, representing a unique core-satellite structure which might facilitate the sustained drug release. Compared with commercial liposomal PTX formulation (Lipusu ® ), PTX@PS exhibited superb tumor cell killing ability underlain by multiple pro-apoptotic mechanisms. Moreover, endocytic process of PTX@PS significantly inhibits drug transporter P-gp expression which could be largely activated by free drug diffusion. In glioma mice models, it has also confirmed that PTX@PS remarkably eradicate tumors, which renders polymersomes as a promising alternative to liposomes as drug carriers in clinic.

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