ABSTRACT
Breast cancer is the most common malignant tumors in females. Although the conventional treatment has demonstrated a certain effect, some limitations still exist. The Rho guanosine triphosphatase (GTPase) Cdc42 (Cell division control protein 42 homolog) is often upregulated by some cell surface receptors and oncogenes in breast cancer. Cdc42 switches from inactive guanosine diphosphate (GDP)-bound to active GTP-bound though guanine-nucleotide-exchange factors (GEFs), results in activation of signaling cascades that regulate various cellular processes such as cytoskeletal changes, proliferation and polarity establishment. Targeting Cdc42 also provides a strategy for precise breast cancer therapy. In addition, Cdc42 is a potential target for several types of non-coding RNAs including microRNAs and lncRNAs. These non-coding RNAs is extensively involved in Cdc42-induced tumor processes, while many of them are aberrantly expressed. Here, we focus on the role of Cdc42 in cell morphogenesis, proliferation, motility, angiogenesis and survival, introduce the Cdc42-targeted non-coding RNAs, as well as present current development of effective Cdc42-targeted inhibitors in breast cancer.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/therapy , Molecular Targeted Therapy , RNA, Untranslated/metabolism , cdc42 GTP-Binding Protein/metabolism , Apoptosis , Breast Neoplasms/blood supply , Breast Neoplasms/pathology , Epithelial Cells/metabolism , Female , Humans , RNA, Untranslated/geneticsABSTRACT
This study was designed to investigate the effect of digoxin on migration and invasion of human gastric carcinoma MKN45 cells and its possible mechanism. MKN45 cells were treated with different concentrations of digoxin for 24 h. The shRNA-AEG-1 plasmid was transfected into MKN45 cells via lipofectamine to block the expression of astrocyte elevated gene-1 (AEG-1). Western blot was used to analyze the protein levels of matrix metalloproteinase-9 (MMP-9), E-cadherin and AEG-1. The result showed that digoxin reduced the abilities of migration and invasion (P < 0.05), up-regulated the protein level of E-cadherin (P < 0.05), and down-regulated the protein levels of MMP-9 and AEG-1 (P < 0.05) in MKN45 cells in a dose-dependent manner. Compared with shControl group, shAGE-1 group showed inhibited cellular migration and invasion, higher expression level of E-cadherin, and lower expression levels of MMP-9 and AEG-1. These results suggest that digoxin suppresses the migration and invasion of human gastric carcinoma MKN45 cells in a dose-dependent manner through inhibiting the expression of AEG-1, and then resulting in the up-regulation of the protein expression of E-cadherin and the down-regulation of the protein expression of MMP-9.
Subject(s)
Cell Adhesion Molecules/metabolism , Cell Movement/drug effects , Digoxin/pharmacology , Gene Expression Regulation, Neoplastic , Stomach Neoplasms/pathology , Antigens, CD , Cadherins/metabolism , Cell Line, Tumor , Down-Regulation , Humans , Matrix Metalloproteinase 9/metabolism , Membrane Proteins , Neoplasm Invasiveness , RNA, Small Interfering/metabolism , RNA-Binding Proteins , Transfection , Up-RegulationABSTRACT
OBJECTIVE: To locate round window area and its related structure on auris transection and CT for anatomical evidence of image diagnosis and clinical operation. METHODS: Fifteen normal head specimen fixed with 10% dehyde were scanned by high-resolution computed tomography on canthomeatal line. CT image (depth 1.00 mm, thick 1.00 mm) was obtained. Temporal bone-centered tissues were taken, decalcified, desiccated and socked with collodion, then embedded and made into sequential transactions (thick 1.00 mm). Lower surface of section was observed by both naked eyes and microscope, then scanned and photographed. Versus CT image, auditory ossicle, osseous semicircular canals, vestibule, round window, niche, cochlea, pyramidal eminence, internal acoustic meatus and cochlear aqueduct were identified respectively. RESULTS: There were 18-22 layers of temporal transection on CT image. Round window and round window niche always appeared on the 10th layer (R) and the 11th layer (L). The mean of the depth of anterior wall was 0.92 mm (R) and 0.90 mm (L), and depth 1.89 mm (R) and 2.04 mm (L). The average distance from niche to jugular fossa wall was 2.10 mm (R) and 2.39 mm (L). No significant difference among of thickness, depth and distance from niche to jugular fossa wall. CONCLUSIONS: Temporal bone transection specimen had a clear picture of anatomical position between round window area and its related structure. Versus CT, the result contributed to image diagnosis and operation on auris diseases.
