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Although giant unilamellar vesicles (GUVs) have been extensively studied as synthetic cell-like microcompartments, their applicability as cytomimetic models is severely compromised by low levels of membrane permeability, low encapsulation efficiencies and high physicochemical instability. Here, we develop an integrated cytomimetic model comprising a macromolecularly crowded interior with high sequestration efficiency and enclosed within a phospholipid membrane that is permeable to molecules below a molecular weight cut-off of ca. 4 kDa. The protocells are readily prepared by spontaneous assembly of a phospholipid membrane on the surface of preformed polynucleotide/polysaccharide coacervate micro-droplets and are designated as giant coacervate vesicles (GCVs). Partial anchoring of the GCV membrane to the underlying coacervate phase results in increased robustness, lower membrane fluidity and increased permeability compared with GUV counterparts. As a consequence, enzyme and ribozyme catalysis can be triggered in the molecularly crowded interior of the GCV but not inside the GUVs when small molecule substrates or inducers are present in the external environment. By integrating processes of membrane-mediated compartmentalization and liquid-liquid microphase separation, GCVs could offer substantial advantages as cytomimetic models, synthetic protocells and artificial biomolecular microreactors. ASSOCIATED CONTENT Supporting Information.The Supporting Information is available free of charge via the Internet at http://pubs.acs.org.Further experimental details, methods, and figures.

Abstract. acts as an oncomiR and is involved in tumor development, progression and metastasis, and confers resistance to chemotherapeutic drugs by targeting a number of molecules in several human cancers. However, the function and underlying molecular mechanism of miR-494 in hepatocellular carcinoma (HCC) has not been totally elucidated. In the present study, we determined the role played by miR-494 in HCC tissues and HCC cell lines using quantitative RT-PCR (RT-qPCR). The results showed that, miR-494 was significantly upregulated in HCC tissues and HCC cell lines. Additionally, a high miR-494 expression positively correlated with tumor differentiation (P<0.01), TNM stage (P<0.01) and lymph node metastasis (P<0.01). Luciferase reporter assays confirmed that miR-494 binds to the 3'-untranslated region (3'-UTR) of the phosphatase and tensin homolog (PTEN) mRNA and represses its translation. Functional analyses indicated that the upregulation of miR-494 promoted cell viability, migration and invasion, decreased cell apoptosis and cell cycle arrest at G1 stage, and conferred sorafenib resistance to HCC cell lines. Underexpression of PTEN by siRNA significantly attenuated the inhibitory effects of anti-miR-494 on the proliferation, migration and invasion of liver cancer cells. Mechanistic investigations revealed that miR-494 suppressed the expression of PTEN but increased the expression of PI3K and p-Akt, which contribute to the promotion of proliferation, migration and invasion, and increased sorafenib resistance to HCC cell lines. These findings suggested that miR-494 is a potential candidate for HCC therapeutics.

A coacervate-in-coacervate micro-architecture is constructed as a multi-compartment protocell model, in which a multi-enzyme cascade is spatially organized for competitive enzymatic reactions.

MicroRNAs (miRNAs) are a class of small non-coding RNAs and have critical roles in tumorigenesis and metastasis. A growing body of evidence showed that microRNA-133a (miR-133a) was downregulated and played tumor suppressor roles in gastric, colorectal, bladder, and lung cancer. However, the role and underlying molecular mechanism of miR-133a in hepatocellular carcinoma (HCC) remain unclear. In this study, we analyzed the expression of miR-133a in HCC tissues and HCC cell lines. We find that miR-133a was downregulated in HCC tissues and cell lines and that miR-133a expression negatively correlated with tumor differentiation (P < 0.01), TNM stage (P < 0.01), and lymph node metastasis (P < 0.01). Then, functional studies demonstrate that restoration of miR-133a in HepG2 cells significantly suppressed proliferation, colony formation, migration, and invasion, induced cell cycle arrest at G0/G1 stage and cell apoptosis in vitro, and decreased tumor size and weight in a nude mouse HepG2 xenograft model. Using bioinformatics method and dual luciferase assays identified insulin-like growth factor 1 receptor (IGF-1R) as a direct target of miR-133a in HCC cells. Furthermore, overexpression of miR-133a inhibited activation AKT and ERK signal pathway, which contributed to suppression of HCC cell growth. These findings suggest that miR-133a may act as a tumor suppressor and inhibited survival of HCC cells by targeting IGF-1R.

Background and objective: ITGA3 is a cell surface adhesion protein that interacts with extracellular matrix proteins which function in cancer metastasis. We examined the relationship of pancreatic ITGA3 expression with the clinical and pathological characteristics of patients with pancreatic cancer. Methods: Data mining was used to analyze pancreatic cancer data from The Cancer Genome Atlas database. A Chi squared test was used to evaluate correlations of ITGA3 expression with clinical and pathological parameters. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of ITGA3 expression. Survival analysis and Cox regression analysis were used to examine the prognostic value of ITGA3 expression. Gene Set Enrichment Analysis (GSEA) was used to identify signaling pathways related to ITGA3 expression. Results: Pancreatic expression of ITGA3 was greater in patients with pancreatic cancer than those without cancer, and was also associated with histological type, histological grade, stage, T classification, vital status, and relapse. ROC analysis indicated that ITGA3 had significant diagnostic value, in that high expression correlated with poor overall survival and relapse-free survival, especially in patients with early-stage cancer. Cox analysis indicated that high ITGA3 expression was an independent prognostic factor for pancreatic cancer. GSEA analysis identified 9 signaling pathways that were enriched in the presence of high ITGA3 expression. Conclusion: Expression of ITGA3 can be used as a diagnostic and prognostic biomarker in pancreatic cancer.

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Abstract. The miR-222 cluster has been demonstrated to function as oncomiR in human hepatocellular carcinoma (HCC). miR-222 confers chemotherapy drug resistance in various cancers, including HCC. However, the effects and mechanisms by which miR-222 regulates liver tumorigenicity and confers sorafenib (SOR) resistance remain unclear. Here we first investigated the miR-222 effect on proliferation, cell cycle, apoptosis, migration and invasion of HCC. Our results demonstrated that miRNA inhibitors specially targeting miR-222 significantly suppressed cellular proliferation, migration, invasion and G1/S transition of the cell cycle, and induced cell apoptosis in HepG2 cells. In addition, we investigated whether miR-222 confers SOR resistance in HepG2 cells to explore it roles in acquisition of drug resistance. The results showed that miR-222 inhibitors induced sensitivity to the antitumor effect of sorafenib in human HepG2 cells. Importantly, our study also showed that miR-222 could regulate the expression of phosphorylation PI3K and AKT, which might contribute to miR-222 conferred SOR resistance in HepG2 cells. In conclusion, this study demonstrates that miR-222 can promote cell proliferation, migration and invasion, and decrease cell apoptosis, as well as enhance the resistance of HCC cells to sorafenib miR-222 through activating the PI3K/AKT signaling pathway.