Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Recent study found an increased level of glypican-1 positive (GPC1 + ) plasma exosomes in patients with stage II CRC, but decreased levels of plasma miR-96-5p and miR-149. This study further investigated the clinical significance of plasma GPC1 + exosomes and plasma miR-96-5p and miR-149 levels in stage III CRC patients. To study the effect of these microRNAs on GPC1 + plasma exosomes, we isolated and purified exosomes and overexpressed human GPC1 and the microRNAs miR-96-5p and miR-149 by adenovirus vectors. Overexpression of GPC1 activated epithelial-mesenchymal transition (EMT) which then increased invasion and migration in HT29 and HCT-116 colon cancer cells. In contrast, silencing GPC1 expression and overexpressing miR-96-5p and miR-149 significantly inactivated EMT and decreased invasion and migration of HT29 and HCT-116 cells. miR-96-5p and miR-149 inhibitors significantly increased invasion and migration of HT29 and HCT-116 cells. Our results indicate that high levels of circulating GPC1 positive exosomes before and after surgery as well as low circulating miR-96-5p and miR-149 before surgery indicated a severe clinical status and poor prognosis in stage III colon cancer patients. We conclude that GPC1 can be a biomarker for relapse of stage III CRC and may be involved in EMT activation, invasion, and migration of colorectal cancer cells.

Three-dimensional (3D) culture has been increasingly used to investigate tumor cell biology for improved simulation of the natural developing environment. However, the way in which 3D culture affects the gene expression and biological functions of glioma cells remains to be fully elucidated. In the present study, 3D culture environments were established using collagen scaffolds with different pore sizes, followed by the comparison of gene expression profiles and associated biological functions of glioma cells, including the U87, U251 and HS683 cell lines, in 3D collagen scaffolds with conventional two-dimensional (2D) cultured cells. Finally, the possible signaling pathways regulating these differences were investigated. It was found that the 3D collagen scaffold culture upregulated the expression of genes associated with stemness, cell cycle, apoptosis, epithelia-mesenchymal transition, migration, invasion and glioma malignancy, and induced the corresponding functional changes. Apoptotic pathways, the Wnt pathway, Sonic Hedgehog pathway and Notch pathway, may be involved in the regulation of these changes. The aperture size of the collagen-scaffold did not appear to affect the gene expression or functions of the glioma cells. The results of the study suggested that the 3D collagen scaffold enhanced the malignancy of glioma cells and may be a promising in vitro platform for investigations of glioma.

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Abstract. Phospholipase C (PLC) is a pivotal enzyme in the phosphoinositide pathway that promotes the second messengers, diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), to participate in eukaryotic signal transduction. Several PLC isozymes are associated with cancer, such as PLC-β1, PLC-δ1, PLC-ε and PLC-γ1. However, the role of PLC-δ3 (PLCD3) in nasopharyngeal carcinoma (NPC) has not been investigated to date. In our previous study, we demonstrated that flotillin2 (Flot2) plays a pro-neoplastic role in NPC and is involved in tumour progression and metastasis. In the present study, we screened the interacting proteins of Flot2 using the yeast two-hybrid (Y2H) method and verified the interaction between PLCD3 and Flot2 by co-immunoprecipitation. We also investigated the biological functions of PLCD3 in NPC. Inhibition of PLCD3 expression impaired the malignant potential of 5-8F, a highly metastatic NPC cell line, by restraining its growth, proliferation, mobility and migration. The present study demonstrated that PLCD3 may be an oncogenic protein in NPC and that it plays an important role in the progression of NPC partially by interacting with Flot2.

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Luminescent net-like inorganic scaffolds with Eu3+-doped hydroxyapatite were firstly synthesized by the one-step hydrothermal method and thiol–ene click reaction.