ABSTRACT
Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in the tumorigenesis and progression of diverse malignancies. However, the majority of circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined and the exact functions and underlying mechanisms of circRNAs in ESCC still need further exploration. In this study, we identified a novel onco-circRNA hsa_circ_0002938, derived from the exons of cysteine-rich transmembrane BMP regulator 1 (CRIM1) pre-mRNA, referred to as circCRIM1. We found that the expression of circCRIM1 was higher in ESCC tissues, compared to para-carcinoma tissues. Increased expression of circCRIM1 was positively correlated with clinical parameters of ESCC patients including tumor-node-metastasis (TNM) stage, tumor invasion range, and lymph node metastasis. Functionally, the results from the experiments in vitro showed that the knockdown of circCRIM1 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in ESCC cells. By conducting bioinformatics algorithms analyses and microRNA (miRNA) rescue experiments, we found that circCRIM1 could act as a competing endogenous RNA (ceRNA) to sponge miR-342-3p in ESCC cells, and thereby upregulated the expression of transcription factor 12 (TCF12), a key regulator promoting the EMT process. Taken together, circCRIM1 facilitates the progression of ESCC by sponging miR-342-3p to regulate TCF12 and promote EMT, and the circCRIM1/miR-342-3p/TCF12 axis may be regarded as a potential predictive biomarker and therapeutic target for treating ESCC.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , MicroRNAs , Humans , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/pathology , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/geneticsABSTRACT
In this study, we investigate the efficacy of SP (Schisandra polysaccharide) in prevention of radiation-induced immune dysfunction and discussed the underlying mechanisms with a Bal/bc mouse model. The data demonstrated that SP could reverse the decreases in the number of white blood cells and lymphocytes in peripheral blood. In addition, the immunoglobulin G (IgG) and complement C3 in blood serum were all decreased after radiation and SP could restore this radiation disorder. Furthermore, SP could reverse the deregulation of CD3(+)CD4(+) and CD3(+)CD8(+) T cell subsets in peripheral blood and thymus of mice after radiotherapy. We also performed terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) and Immunohistochemistry (IHC) to investigate the apoptosis and underlying mechanisms of SP in thymus. Data showed that radiation-induced apoptosis of thymocytes could be reversed by SP through inducing upregulation of Bcl-2 expression and downregulation of Fas and Bax levels. Furthermore, SP has no any side-effects on immunity of normal mice. In conclusion, our results indicated that SP could effectively prevent immune injury during radiotherapy by protecting the immune system. This valuable information should be of assistance in choosing a rational design for therapeutic interventions of prevention immune system damage in the radiation treatment.
Subject(s)
Immune System/drug effects , Immune System/radiation effects , Plant Extracts/pharmacology , Polysaccharides/pharmacology , Radiation-Protective Agents/pharmacology , Radiation , Schisandra/chemistry , Animals , Complement C3 , Gene Expression Regulation/drug effects , Immunoglobulin G/blood , Lymphocyte Count , Lymphocytes/drug effects , Lymphocytes/immunology , Lymphocytes/metabolism , Lymphocytes/radiation effects , Male , Mice , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , T-Lymphocyte Subsets/radiation effects , Thymocytes/drug effects , Thymocytes/radiation effects , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism , fas Receptor/genetics , fas Receptor/metabolismABSTRACT
A uniform plano-convex spherical microlens array with a long focal length was fabricated by combining the micromilling and injection molding processes in this work. This paper presents a quantitative study of the injection molding process parameters on the uniformity of the height of the microlenses. The variation of the injection process parameters, i.e., barrel temperature, mold temperature, injection speed, and packing pressure, was found to have a significant effect on the uniformity of the height of the microlenses, especially the barrel temperature. The filling-to-packing switchover point is also critical to the uniformity of the height of the microlenses. The optimal uniformity was achieved when the polymer melts completely filled the mold cavity, or even a little excessively filled the cavity, during the filling stage. In addition, due to the filling resistance, the practical filling-to-packing switchover point can vary with the change of the filling processing conditions and lead to a non-negligible effect on the uniformity of the height of the microlenses. Furthermore, the effect of injection speed on the uniformity of the height of the microlenses was analyzed in detail. The results indicated that the effect of injection speed on the uniformity of the height of the microlenses is mainly attributed to the two functions of injection speed: transferring the filling-to-packing switchover point and affecting the distribution of residual flow stress in the polymer melt.