ABSTRACT
BACKGROUND: Circular RNAs (circRNAs) are involved in the progression of colon cancer (CC). This study aimed to examine the role of a new circRNA circ_0101050 in CC. METHODS: Dual-luciferase reporter and RNA immunoprecipitation analyses were performed to validate the target relationships among maternal embryonic leucine zipper kinase (MELK), microRNA (miR)-140-3 p, and circ_0101050. Expression levels were calculated using western blotting and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blotting was performed to evaluate the relative expression of Bcl-2 and Bax proteins to determine cell death. Cell Counting Kit-8 (CCK-8) and colony formation assays were performed to determine the proliferative potential of CC cells. The migration rate of CC cells was evaluated using wound healing assays. Tumor formation tests were performed to determine the effect of circ_0101050 on tumor development in vivo. RESULTS: Elevated levels of circ_0101050 and MELK were observed in CC. By inhibiting circ 0,101,050 or MELK, CC cell proliferation and migration were inhibited, but CC cell apoptosis was promoted. Silencing circ_0101050 also inhibited CC growth in vivo. We also found that miR-140-3 p was downregulated, which alleviated the repressive effects of circ_0101050 knockdown on proliferating and migrating CC cells, as well as the stimulating effect on apoptosis. In addition, the absence of MELK alleviated the effects of miR-140-3 p downregulation, which enhanced CC cell malignancy. CONCLUSIONS: Circ_0101050 exacerbates malignant phenotypes in CC by targeting the miR-140-3 p/MELK axis. These findings suggested that the circ_0101050/miR-140-3 p/MELK network may be a prospective target for CC treatment.
ABSTRACT
Cardiac hypertrophy, a major determinant of heart failure, is associated with heat shock proteins (HSPs). HSP75 has been reported to protect against environmental stresses; however, its roles in cardiac hypertrophy remain unclear. Here, we generated cardiac-specific inducible HSP75 transgenic mice (TG) and cardiac hypertrophy was developed at 4 weeks after aortic banding in TG mice and wild-type littermates. The results revealed that overexpression of HSP75 prevented cardiac hypertrophy and fibrosis as assessed by heart weight/body weight ratio, heart weight/tibia length ratio, echocardiographic and hemodynamic parameters, cardiomyocyte width, left ventricular collagen volume, and gene expression of hypertrophic markers. Further studies showed that overexpression of HSP75 inhibited the activation of TAK/P38, JNK, and AKT signaling pathways. Thus, HSP75 likely reduces the hypertrophy and fibrosis induced by pressure overload through blocking TAK/P38, JNK, and AKT signaling pathways.
Subject(s)
Cardiomegaly/genetics , HSP90 Heat-Shock Proteins/genetics , Myocardium/pathology , Recombinant Proteins/genetics , Animals , Atrial Natriuretic Factor/genetics , Atrial Natriuretic Factor/metabolism , Body Weight , Cardiomegaly/metabolism , Cardiomegaly/pathology , Cell Size , Collagen/metabolism , Fibrosis , HSP90 Heat-Shock Proteins/metabolism , Heart Ventricles/metabolism , Humans , MAP Kinase Signaling System , Mice , Mice, Inbred C57BL , Mice, Transgenic , Muscle Cells/metabolism , Muscle Cells/pathology , Myocardium/metabolism , Myosin Heavy Chains/genetics , Myosin Heavy Chains/metabolism , Organ Size , Phosphorylation , Recombinant Proteins/metabolism , Transcription, Genetic , Ventricular Pressure , Ventricular RemodelingABSTRACT
OBJECTIVE: To investigate the utilization of fuzzy matter - element model in evaluating the promoting effects of transdermal enhancers. METHOD: Paracetamol was used as drug model. Azone, menthol, camphor, oleic acid, clove oil, Schizonepeta tenuifolia oil and patchouli were used as transdermal enhancers. Transdermal absorption experimentation of paracetamol was detected on the device of penetrating skins of rabbit in vitro and penetrating rates, steady fluxs, lag time and enhancement ratio were calculated to evaluate promoting effects of transdermal enhancers with fuzzy matter-element model based on variation coefficient weight. RESULT: Paracetamol had the best promoting function with 2% clove oil and 2% camphor. The function drops slightly with 1% azone, 2% Schizonepeta tenuifolia oil, 2% menthol and 2% oleic acid ranked behind. The worst was with 2% patchouli. CONCLUSION: Fuzzy matter-element model based on variation coefficient weight could judge the promoting and penetrating effect of transdermal enhancers objectively and feasible.
