Search results for "Gene silencing"

Embryonic adhesion is not affected by endometrial leptin receptor gene silencing.

2006

Objective In rodents, evidence suggests that the leptin system is mandatory for embryonic implantation. We aimed to investigate the functional relevance of the endometrial leptin receptor (OB-R) in the adhesion phase of human implantation. Design We used an in vitro model for embryonic adhesion, composed of a human endometrial cell line (HEC1-A) and B6C3F1 mouse embryos. The OB-R gene was silenced in a stable manner by RNA interference, and embryonic adhesion rates were analyzed. Setting Research laboratory at a university-affiliated center. Intervention(s) RNA interference. Main Outcome Measure(s) Embryonic adhesion in cells treated with OB-R RNAi. Result(s) The OB-R shRNA-transfected cell…

The histone acetyltransferase MOF activates hypothalamic polysialylation to prevent diet-induced obesity in mice

2014

Overfeeding causes rapid synaptic remodeling in hypothalamus feeding circuits. Polysialylation of cell surface molecules is a key step in this neuronal rewiring and allows normalization of food intake. Here we examined the role of hypothalamic polysialylation in the long-term maintenance of body weight, and deciphered the molecular sequence underlying its nutritional regulation. We found that upon high fat diet (HFD), reduced hypothalamic polysialylation exacerbated the diet-induced obese phenotype in mice. Upon HFD, the histone acetyltransferase MOF was rapidly recruited on the St8sia4 polysialyltransferase-encoding gene. Mof silencing in the mediobasal hypothalamus of adult mice prevented…

Molecular Effects of the CTG Repeats in Mutant Dystrophia Myotonica Protein Kinase Gene

2008

Myotonic Dystrophy type 1 (DM1) is a multi-system disorder characterized by muscle wasting, myotonia, cardiac conduction defects, cataracts, and neuropsychological dysfunction. DM1 is caused by expansion of a CTG repeat in the 3 untranslated region (UTR) of the Dystrophia Myotonica Protein Kinase (DMPK) gene. A body of work demonstrates that DMPK mRNAs containing abnormally expanded CUG repeats are toxic to several cell types. A core mechanism underlying symptoms of DM1 is that mutant DMPK RNA interferes with the developmentally regulated alternative splicing of defined pre-mRNAs. Expanded CUG repeats fold into ds(CUG) hairpins that sequester nuclear proteins including human Muscleblind-lik…

Apollon gene silencing induces apoptosis in breast cancer cells via p53 stabilisation and caspase-3 activation

2009

We analysed the effects of small interfering RNA (siRNA)-mediated silencing of Apollon, a member of the inhibitors of apoptosis protein family, on the proliferative potential and ability of human breast cancer cell lines to undergo apoptosis. In wild-type p53 ZR75.1 cells, Apollon knockdown resulted in a marked, time-dependent decline of cell growth and an increased rate of apoptosis, which was associated with p53 stabilisation and activation of the mitochondrial-dependent apoptotic pathway. Pre-incubation of cells with a p53-specific siRNA resulted in a partial rescue of cell growth inhibition, as well as in a marked reduction of the apoptotic response, indicating p53 as a major player in …

Improvements in Rational Design Strategies of Inulin Derivative Polycation for siRNA Delivery.

2016

The advances of short interfering RNA (siRNA)-mediated therapy provide a powerful option for the treatment of many diseases, including cancer, by silencing the expression of targeted genes involved in the progression of the pathology. On this regard, a new pH-responsive polycation derived from inulin, Inulin-g-imidazole-g-diethylenetriamine (INU-IMI-DETA), was designed and employed to produce INU-IMI-DETA/siRNA "Inulin COmplex Nanoaggregates" (ICONs). The experimental results showed that INU-IMI-DETA exhibited strong cationic characteristics and high solubility in the pH range 3-5 and self-aggregation triggered by pH increase and physiological salt concentration. INU-IMI-DETA showed as well…

Study of the interactions between Broad bean wilt virus 1 and its host plants

Broad bean wilt virus 1 (BBWV-1) is the type member of the Fabavirus genus, in the Secoviridae family. BBWV-1 is worldwide distributed and infects important horticultural and ornamental crops causing considerable economic losses. However, information about the biological and molecular characteristics of BBWV-1 isolates is scarce. BBWV-1 is composed of two molecules of positive single-stranded RNA (ssRNA+) that are separately encapsidated in virions of icosahedral morphology. Each ssRNA+ encodes polyproteins which are processed by proteolytic cleavage into functional peptides. RNA1 (~ 5.8 kb) encodes for one polyprotein that renders proteins involved in viral replication: a protease cofactor…