Neuroblastoma (NB) is the most common extracranial solid tumor derived from neural crest in children. Recently, the role of miRNA has been studied extensively in the development of NB. Here, we investigated the clinical significance of microRNA-490-5p (miR-490-5p) in NB. A total of 72 pairs of NB tumor tissues and matched adjacent normal nerve tissues were collected from NB patients. The expression of miR-490-5p was significantly down-regulated in NB tissues and cell lines using quantitative real-time PCR. Using Pearson Chi-square test and Kaplan-Meier analysis, we found that significantly decreased miR-490-5p levels were correlated with INSS stage, lymph-node metastasis, and poor survival prognosis in NB patients. MiR-490-5p overexpression significantly suppressed cell proliferation migration, invasion, and induced cell cycle G0/G1 arrest and cell apoptosis in NB cell lines (SH-SY5Y and SK-N-SH) using CCK-8, flow cytometry, and transwell assays. Mechanistically, MYEOV was confirmed as a target gene of miR-490-5p by luciferase reporter assay. Furthermore, MYEOV knockdown imitated, while overexpression rescued the changes in the biological features of miR-490-5p on NB cells. Our results demonstrated for the first time that miR-490-5p functions as a tumor suppressor in NB by targeting MYEOV, which might provide novel approaches for the treatment of NB.
MicroRNAs/genetics , Molecular Targeted Therapy , Neuroblastoma/genetics , Proto-Oncogene Proteins/genetics , Child , Humans
BACKGROUND: Urocortin (UCN) is a newly identified vascular-active peptide that has been shown to reverse cardiovascular remodeling and improve left ventricular (LV) function. The effects and mechanism of urocortin 2 (UCN2) in vivo on the electrical remodeling of left ventricle and the hemodynamics of hypertensive objectives have not been investigated. METHODS: UCN2 (1 µg/kg/d, 3.5 µg/kg/d or 7 µg/kg/d) was intravenously injected for 2 weeks and its effects on hemodynamics in spontaneously hypertensive rats (SHRs) observed. The whole-cell patch clamp technique was used to explore the effects of UCN2 on the electrical remodeling of left ventricular cardiomyocytes. The flow cytometry method was used to determine the content of fluorescence calcium in myocardium. RESULTS: UCN2 improved the systolic and diastolic function of SHRs as demonstrated by decreased left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), increased +dp/dtmax and -dp/dtmax and decreased cAMP level. UCN2 inhibited the opening of L-type calcium channel and decreased the calcium channel current of cardiomyocytes. In addition, UCN2 also decreased the contents of fluorescence calcium in SHR myocardium. However, astressin2-B (AST-2B), the antagonist of corticotropin-releasing factor receptor 2 (CRFR2), could reverse the inhibitory effects of UCN2 on calcium channel. CONCLUSION: UCN2 can modulate electrical remodeling of the myocardium and hemodynamics in an experimental model of SHR via inhibition of L-type calcium channel and CRFR2 in cardiomyocytes.
Calcium Channels, L-Type/physiology , Corticotropin-Releasing Hormone/pharmacology , Hemodynamics/drug effects , Receptors, Corticotropin-Releasing Hormone/physiology , Urocortins/pharmacology , Animals , Atrial Remodeling/drug effects , Atrial Remodeling/physiology , Calcium/metabolism , Corticotropin-Releasing Hormone/physiology , Dose-Response Relationship, Drug , Hemodynamics/physiology , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Myocardium/metabolism , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/physiology , Peptide Fragments/pharmacology , Peptides, Cyclic/pharmacology , Rats , Rats, Inbred SHR , Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors , Urocortins/physiology , Ventricular Function, Left/drug effects , Ventricular Function, Left/physiology
The objective of this study is to investigate lysosome-associated protein transmembrane 4b-35 (LAPTM4B-35) protein expression in gastric cancer and its clinical implications. LAPTM4B-35 protein expression in 652 gastric cancer specimens and matched adjacent non-cancerous tissues was evaluated by immunohistochemical staining. Subsequently, the relationship between LAPTM4B-35 protein expression, clinical pathological parameters, and prognosis of gastric cancer was determined. LAPTM4B-35 protein expression was significantly higher in gastric cancer tissue compared to adjacent non-cancerous tissues (P = 0.001). In total, 417 (63.96 %) of the 652 gastric cancer cases demonstrated high LAPTM4B-35 protein expression. Multiple regression analysis was performed to identify the factors related to lymph node metastasis. As a result, age, tumor number, primary tumor category, histological type, histological growth pattern, and LAPTM4B-35 protein expression were found to be significantly related to lymph node metastasis (P = 0.010, 0.001, 0.032, 0.001, 0.001, and 0.001, respectively). Survival analysis identified that LAPTM4B-35 protein expression was also an independent prognostic factor (P = 0.001). LAPTM4B-35 was highly expressed in gastric cancer and may be a potential target for the management of gastric cancer.
Membrane Proteins/metabolism , Oncogene Proteins/metabolism , Stomach Neoplasms/metabolism , Adult , Aged , Female , Gene Expression , Humans , Immunohistochemistry , Lymphatic Metastasis , Male , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/genetics , Middle Aged , Molecular Targeted Therapy , Neoplasm Grading , Neoplasm Staging , Oncogene Proteins/antagonists & inhibitors , Oncogene Proteins/genetics , Prognosis , Stomach Neoplasms/drug therapy , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Tumor Burden
