Endocrine Abstracts

Objective and methods: Recent studies suggest that altered alternative splicing and, consequently, appearance of an abnormal splicing pattern and even of aberrant/oncogenic splicing-variants, represent a common molecular feature of most tumor pathologies, including Pituitary Neuroendocrine Tumors (PitNETs). However, the putative alteration, pathophysiological role and potential therapeutic utility of splicing machinery components [i.e. spliceosome-components (SCs) and splicing...

There is increasing evidence that alterations in alternative splicing can be linked to key tumor features in cancer. Dysregulations in the splicing machinery constitute the underlying cause in many of these alterations and, consequently, splicing and its control are emerging as a novel and transversal cancer hallmark, due to its association with different dysfunctions of tumor cells. In line with this, we discovered the existence of aberrantly spliced variants of somatostatin ...

Somatostatin (SST)-system is a pleiotropic hormonal system composed by several ligands/receptors that is involved in the regulation of multiple pathophysiological functions. Specifically, certain components of the SST-system are dysregulated in several endocrine-related cancer types compared to control tissues, wherein these alterations seem to influence their development/progression. However, the presence and functional role of neuronostatin (NST) and its putative G-protein c...

Dysregulation of the splicing machinery is emerging as a novel cancer hallmark due to its association with multiple dysfunctions in tumor cells. An inappropriate function of the components of this machinery (spliceosome) could be primarily linked with the generation of tumor-associated aberrant splicing variants. In line with this, we have previously reported that overexpression of aberrantly spliced variants of somatostatin receptor 5 (sst5TMD4) and ghrelin (In1-ghrelin) is d...

: Hepatic steatosis is a common obesity-associated pathology characterized by the accumulation of fat within the liver, which can progress to liver fibrosis, cirrhosis and ultimately lead to hepatocellular carcinoma. Remarkably, obesity and cancer course with a profound dysregulation of the genetic expression patterns and, particularly, with the aberrant expression of splicing variants that could contribute to the aggressiveness and comorbidities of these pathologies. Since th...

: Prostate cancer (PCa) is the most common cancer among men in developed countries. Unfortunately, the heterogeneity of this malignancy hinders the finding of new biomarkers and therapeutic tools. A potential factor contributing to PCa is alternative splicing, which can generate the appearance of oncogenic variants involved in PCa aggressiveness. Thus, we hypothesized that the alteration of the splicing machinery (spliceosome components and splicing factors (SFs)) could be ass...

Prevalence of metabolic syndrome (MetS) and type-2 Diabetes (T2D) is growing dramatically worldwide. Loss of phenotypic flexibility, i.e. the difficulty to cope with different stressors to maintain metabolic homeostasis, contributes critically to the development of MetS/T2DM. Thus, it is essential to identify the key modifiers of phenotypic plasticity that define an individual’s susceptibility to develop T2DM. In this scenario, emerging evidence indicates that, under adve...

Somatostatin is a pleiotropic neuropeptide that governs multiple biological targets, including tumor cell function, through a family of G protein-coupled receptors with 7-transmembrane domains (TMD), named sst1-5. However, we recently discovered sst5TMD4, an aberrantly spliced, truncated (only 4-TMDs) sst5-variant displaying unique molecular/functional features. sst5TM4 is overexpressed in various endocrine-related tumors exacerbating their malignant characteristics. Here, we ...

Obesity, a disease that is growing at epidemic proportions worldwide, is caused by a combination of genetic and lifestyle factors. One of the most common pathologies associated with obesity is hepatic steatosis, an accumulation of fat within the liver that can progress to liver fibrosis, cirrhosis, and ultimately lead to hepatocellular carcinoma. There is emerging evidence that alternative mRNA splicing, the key mechanism providing transcript and protein diversity, is dysregul...

Dietary fat influences systemic inflammatory status, which, in turn, determines the progression of age-associated diseases. Peripheral blood mononuclear cells (PBMCs) comprise a subset of white blood cells placed at the crossroad between diet and inflammation, in that they play a key role in the immune/inflammatory system and their gene expression pattern is influenced by diet. Since the somatostatin (SST), cortistatin (CORT) and ghrelin systems have been shown to modulate the...