Lipid-hybrid cell-derived biomimetic functional materials: A state-of-the-art multifunctional weapon against tumors.

Tumors are among the leading causes of death worldwide. Cell-derived biomimetic functional materials have shown great promise in the treatment of tumors. These materials are derived from cell membranes, extracellular vesicles and bacterial outer membrane vesicles and may evade immune recognition, improve drug targeting and activate antitumor immunity. However, their use is limited owing to their low drug-loading capacity and complex preparation methods. Liposomes are artificial bionic membranes that have high drug-loading capacity and can be prepared and modified easily. Although they can overcome the disadvantages of cell-derived biomimetic functional materials, they lack natural active targeting ability. Lipids can be hybridized with cell membranes, extracellular vesicles or bacterial outer membrane vesicles to form lipid-hybrid cell-derived biomimetic functional materials. These materials negate the disadvantages of both liposomes and cell-derived components and represent a promising delivery platform in the treatment of tumors. This review focuses on the design strategies, applications and mechanisms of action of lipid-hybrid cell-derived biomimetic functional materials and summarizes the prospects of their further development and the challenges associated with it.

MiR-18b suppresses high-glucose-induced proliferation in HRECs by targeting IGF-1/IGF1R signaling pathways.

MicroRNAs (miRNAs) are important for the proliferation of endothelial cells and have been shown to be involved in diabetic retinopathy (DR). In previous study, we found that miRNAs might play a critical role in hyperglycemia-induced endothelial cell proliferation based on miRNA expression profiling. Here, the roles of microRNA-18b (miR-18b) in the proliferation of human retinal endothelial cells (HRECs) were investigated in an in vitro model of HRECs grown in high glucose. We identified that levels of miR-18b were decreased in high-glucose-induced HRECs, compared with those in cells incubated in normal glucose. However, the reduction of miR-18b up-regulated vascular endothelial growth factor (VEGF) secretion and promoted effects on in vitro proliferation of HRECs. Mechanistically, insulin growth factor-1 (IGF-1) was identified as a target of miR-18b. IGF-1 simulation could antagonize the effect induced by miR-18b up-regulation, promoting cell proliferation and increasing VEGF production. In contrast, the opposite results were observed with silencing IGF-1, which was consistent with the effects of miR-18b overexpression. MiR-18b exerted its function on VEGF synthesis and cell proliferation by suppressing the IGF-1/insulin growth factor-1 receptor (IGF1R) pathway, consequently inhibiting the downstream phosphorylation of Akt, MEK, and ERK. Hence, this may provide a new insight into understanding the mechanism of DR pathogenesis, as well as a potential therapeutic target for proliferative DR.

FOXC2 promotes colorectal cancer proliferation through inhibition of FOXO3a and activation of MAPK and AKT signaling pathways.

Abnormal expression of FOXC2 has been found in several human cancers. However, the role of FOXC2 in the progression of colorectal cancer (CRC) has not been well characterized. In analysis of 206 CRC specimens, we revealed that both high expression and nuclear localization of FOXC2 were correlated to aggressive characteristics and poor survival of patients with CRC. FOXC2 promoted cell proliferation through activation of MAPK and AKT pathways, subsequently down-regulating p27, up-regulating cyclin D1 and p-FOXO3a. Furthermore, FOXC2 nuclear localization was required for its promotion of cell proliferation. These findings suggest that FOXC2 plays an essential role in CRC progression and may serve as a valuable clinical prognostic marker of this disease.

HOXB7 as a prognostic factor and mediator of colorectal cancer progression.

PURPOSE: This study was to investigate the clinicopathologic significance and potential role of HOXB7 in the development and progression of colorectal cancer (CRC). EXPERIMENTAL DESIGN: The relationship between HOXB7 expression and clinical characteristics of CRC was analyzed in 224 paraffin-embedded archived CRC specimens by immunohistochemistry (IHC). The effects of HOXB7 on cell growth and proliferation, as well as on tumorigenesis, were examined both in vitro and in vivo, using MTT assay, colony formation assay, cell cycle analysis, soft agar assay, and tumorigenesis in nude mice. Western blotting and real-time reverse transcriptase-PCR were performed to examine the impact of HOXB7 on the PI3K/Akt and MAPK signaling pathways. RESULTS: HOXB7 protein level was significantly correlated with advanced Dukes stage (P < 0.001), T stage (P = 0.012), distant metastasis (P = 0.042), higher proliferation index (P = 0.007) and poor survival of patients (P = 0.005). Enforced expression of HOXB7 in CRC cell lines significantly enhanced cell growth, proliferation and tumorigenesis. Conversely, knockdown of HOXB7 caused an inhibition of cell growth, proliferation, and tumorigenesis. We also showed that HOXB7 accelerated G(0)-G(1) to S-phase transition concomitantly with upregulation of cyclin D1 and downregulation of p27Kip1. On the contrary, knockdown of HOXB7 caused G(1)-S-phase arrest, downregulation of cyclin D1 and upregulation of p27Kip1. Enforced expression of HOXB7 could enhance PI3K/AKT and MAPK pathway activity. CONCLUSION: Our findings suggest that HOXB7 protein, as a valuable marker of CRC prognosis, plays an important role in the development and progression of human CRC.