ABSTRACT
MicroRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level which have been reported to be involved in the pathogenesis of various cancers. In the present study, we found that miR-497 was downregulated in osteosarcoma tissues. Gain and loss of function studies were carried out to investigate the effect of miR-497 on the growth of osteosarcoma cells. The results indicated that miR-497 inhibited the growth of osteosarcoma cells. Furthermore, bioinformatics analysis predicted plexinA4 and CDK6 as targets of miR-497, which was afterward confirmed by luciferase activity assay and rescue experiments. These findings suggested that miR-497, plexinA4 and CDK6 may serve as novel potential makers for osteosarcoma diagnostics and therapy.
Subject(s)
Bone Neoplasms , Cyclin-Dependent Kinase 6/genetics , MicroRNAs/genetics , Osteosarcoma , Receptors, Cell Surface/genetics , Bone Neoplasms/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Invasiveness/genetics , Osteosarcoma/geneticsABSTRACT
OBJECTIVE: Pancreatic carcinoma (PC) is a serious malignancy associated with high morbidity and mortality rates. Previous studies have identified various microRNAs (miRNAs) involved in the development of PC; however, the role of miR-383 still remains unclear. This study investigates the role of miR-383 in the malignant transformation of PC. MATERIALS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to quantify miR-383 and Grb2 associated binding protein 1 (GAB1) RNA levels, and Western blot analysis was performed to measure protein expression. The ability of miR-383 to bind and regulate the expression of GAB1 was assessed using a Luciferase reporter assay. Cell Counting Kit-8 (CCK-8) experiments and flow cytometry analysis were used to assess cell proliferation and apoptosis, respectively. RESULTS: Down-regulation of miR-383 was associated with adverse clinical results and poor prognosis in PC patients. Mechanistically, miR-383 inhibited cell proliferation and promoted apoptosis of PANC-1 (human pancreatic cancer cell) cells. Our results show that miR-383 can act directly on GAB1 to inhibit its expression in PC. This downregulation of GAB1 limits cell proliferation and induced apoptosis of PANC-1 cells. CONCLUSIONS: MiR-383 suppresses tumor development and progression through the downregulation of GAB1 expression.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Pancreatic Neoplasms/genetics , Apoptosis/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Down-Regulation , Humans , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Transfection , Pancreatic NeoplasmsABSTRACT
The effects of sennosides (Sen, an extract of Chinese rhubarb) on cellular spontaneous electric activities of guinea pig taenia coli were studied by intracellular microelectrode technique. Sen 0.1-20 mmol.L-1 improved the depolarization of cell membrane, quickened the burst of slow wave potential, and increased notably the frequency of spike potentials. Sen (20 mmol.L-1) induced spontaneous spike potentials. These results provide direct evidence for the enhancing effect of Sen on intestinal peristalsis at cellular level.
Subject(s)
Anthraquinones/pharmacology , Muscle, Smooth/physiology , Action Potentials/drug effects , Animals , Colon/physiology , Female , Guinea Pigs , In Vitro Techniques , Male , Muscle, Smooth/cytology , Senna Extract , SennosidesABSTRACT
Experiments have shown that Dachengqi Decoction can inhibit the activity of G-germs which commonly grow in the intestinal tract, inactivate the endotoxin directly in vitro, reduce the amplitude of fever caused by endotoxin injected intravenously, promote the gastric secretion and gastric retaining in rats, and increase the level of glycogen in liver. It also has some other effects. All these actions contribute to the explanation on the efficacy of Dachengqi Decoction to purge off the internal heat.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Animals , Bile/metabolism , Drugs, Chinese Herbal/therapeutic use , Endotoxins , Enterobacteriaceae/drug effects , Female , Fever/chemically induced , Fever/drug therapy , Gastric Juice/metabolism , Glycogen/metabolism , Leukocyte Count/drug effects , Limulus Test , Liver/metabolism , Male , Microbial Sensitivity Tests , Rabbits , Rats , Rats, WistarABSTRACT
The effects of Dachengqi decoction (DCQ) and Rhubarb (Rb) on spontaneous cellular electrical activities of guinea-pig's taenia coli has been studied by intracellular microelectrode technique. DCQ and Rb could both improve depolarization of cell membrane, speed up the burst of slow wave potential (when drug concentration was 1%, P > 0.05; 10% or 20%, P < 0.05), which was dose dependent. At the same concentration, the effects of Rb were more significant than that of DCQ. These results suggested that DCQ and Rb enhanced directly the cellular electrical excitability so as to strengthen the contraction of colon, is one of the mechanisms of these drugs in cellular level on diarrhea action. The ionic basis of the effects might be that DCQ and Rb reduced the K+conductance of cell membrane in rest state.
