The lncRNA GAS5 plays a significant role in tumorigenicity and progression of breast cancer (BC). In this review, we first summarize the role of GAS5 in cell biology, focusing on its expression data in human normal tissues. We present data on GAS5 expression in human BC tissues, highlighting its downregulation in all major BC classes. The main findings regarding the molecular mechanisms underlying GAS5 dysregulation are discussed, including DNA hypermethylation of the CpG island located in the promoter region of the gene. We focused on the action of GAS5 as a miRNA sponge, which is able to sequester microRNAs and modulate the expression levels of their mRNA targets, particularly those involved in cell invasion, apoptosis, and drug response. In the second part, we highlight the translational implications of GAS5 in BC. We discuss the current knowledge on the role of GAS5 as candidate prognostic factor, a responsive molecular therapeutic target, and a circulating biomarker in liquid biopsies with clinical importance in BC. The findings position GAS5 as a promising druggable biomolecule and stimulate the development of strategies to restore its expression levels for novel therapeutic approaches that could benefit BC patients in the future.
Long non-coding RNAs (lncRNAs) and microRNAs are involved in numerous physio-pathological conditions included cancer. To better understand the molecular mechanism of the oral antitumor multikinase inhibitor sorafenib, we profiled the expression of a panel of lncRNAs and miRNAs by qPCR array in a sorafenib-treated hepatocellular carcinoma (HCC) cell line. Among the most affected ncRNAs, we found that sorafenib mediated the dysregulation of the lncRNAs GAS5, HOTTIP and HOXA-AS2 and the miR-126-3p, in a panel of human cancer cell lines (HCC, renal and breast carcinomas). By luciferase gene reporter assay, we discovered that GAS5 may act as a sponge for miR-126-3p in HCC cells. The expression level of GAS5 and miR-126-3p was verified in human liquid and/or solid biopsies from HCC patients. miR-126-3p expression in HCC tissues was decreased respect to their correspondent peritumoral tissues. The levels of plasmatic circulating miR-126-3p and GAS5 were significantly higher and lower in HCC patients compared to healthy subjects, respectively. This study highlighted the capability of sorafenib to modulate the expression of a wide range of ncRNAs and specifically, GAS5 and miR-126-3p were involved in the response to sorafenib of different cancer cell types.
At present, transcatheter aortic valve implantation (TAVI) is a proven treatment option for patients with symptomatic degenerative aortic stenosis at high risk for conventional surgery. In countries where TAVI is currently performed, the number of procedures and centers involved has been continuously increasing. The present document from the Italian Society of Interventional Cardiology (SICI-GISE) aims to improve the available evidence and current consensus on this topic through the definition of training needs and knowledge base for both operators and centers.
the association between C-Reactive Protein (CRP) levels following PPCI and clinical outcome in patients at our tertiary referral centre.Methods: All patients accepted for PPCI between September 2009 and November 2011 were eligible for inclusion.Patient data were obtained from Cardiac Services Database System (Phillips CVIS), and mortality data from the Summary Care Record (SCR) database.Patient characteristics and clinical outcomes were compared according to CRP groups: low (≤10 mg/L), intermediate (10-50 mg/L), and high (>50 mg/L).Continuous variables were compared using oneway ANOVA.Categorical variables were compared using the chi-squared test.A p-value of <0.05 was taken to indicate statistical significance.Results: 1299 of 1877 eligible patients had a recorded CRP and were analysed.Patients in the high CRP group were more likely to be female (32.6% vs. 23.1%,p 0.024) and older (mean age 67.3±14.1 vs. 63.8±12.5 years, p 0.011).Other characteristics were similar across groups (hypertension, diabetes mellitus, previous MI, CABG).30-day mortality was significantly higher in the high group compared to the low group (1.3% vs. 16.7%,p <0.0001), as was overall mortality (hazard ratio 1.8, 95% CI 1.3-2.8)during a mean follow-up period of 2.1 years (Figure 1). Figure 1.Kaplan-Meier Survival CurveConclusions: Our large-cohort retrospective study suggests that elevated CRP at PPCI is associated with significantly higher long-term mortality.Further work is required on strategies to modify inflammatory response following STEMI and improve clinical outcomes following PPCI.
