RESUMO
The present study aimed to explore the biological functions and molecular mechanisms of the long noncoding RNA VIM antisense RNA 1 (VIMAS1) in gastric cancer (GC). The expression of VIMAS1 was analyzed in tissues from patients with GC and GC cell lines by reverse transcriptionquantitative (RTq)PCR. The relationship between VIMAS1 expression and overall survival time of patients with GC was also assessed. To determine the biological functions of VIMAS1, Cell Counting Kit8 assay, colony formation assay, flow cytometry, wound healing assay and Transwell assay were employed. The targeting relationship among VIMAS1, microRNA (miR)8052 and frizzled 1 (FZD1) was verified by the dual luciferase reporter gene assay. The underlying molecular mechanism of VIMAS1 on GC was determined by RTqPCR and western blotting. In addition, tumor formation was detected in nude mice. The results of the present study demonstrated that VIMAS1 was highly expressed in GC tissues and cells. In addition, VIMAS1 expression was demonstrated to be closely related to the prognosis of patients with GC. Notably, silencing VIMAS1 inhibited the proliferation, migration and invasion, and enhanced apoptosis of AGS and HGC27 cells. Silencing VIMAS1 significantly increased the protein expression levels of cleaved caspase3, Bax and Ecadherin, but decreased the protein expression levels of Bcl2, Ncadherin, vimentin, matrix metalloproteinase (MMP)2, MMP9, ßcatenin, cyclin D1, Cmyc and FZD1. Additionally, silencing VIMAS1 inhibited tumor growth in nude mice. Cumulatively, the present study demonstrated that VIMAS1 may promote cell proliferation, migration, invasion and epithelialmesenchymal transition by regulating FDZ1 and activating the Wnt/ßcatenin pathway in GC.
Assuntos
Neoplasias Gástricas/genética , Vimentina/genética , Adulto , Idoso , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , China , DNA Antissenso/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Neoplasias Gástricas/metabolismo , Vimentina/metabolismo , Via de Sinalização Wnt/genética , beta Catenina/metabolismoRESUMO
Proprotein convertase-subtilisin/kexin type 9 (PCSK9) monoclonal antibody is a new therapy to reduce low-density lipoprotein cholesterol (LDL-C) level in patients with familial hypercholesterolemia (FH). This pooled analysis aimed to estimate the efficacy and safety of PCSK9 antibody therapy in FH. Reports of randomized controlled trials (RCTs) comparing PCSK9 antibody to placebo were retrieved by a search of MEDLINE via PubMed, EMBASE, the Cochrane Library databases, ClinicalTrials.gov and Clinical Trial Results (up to November 30, 2015) with no language restriction. Data were abstracted by a standardized protocol. We found eight RCTs (1,879 patients with FH) for the pooled analysis. As compared with placebo, PCSK9 antibody therapy remarkably reduced LDL-C level (mean reduction: -48.54 %, 95 % CI: -53.19 to -43.88), total cholesterol (mean reduction: -31.08%, 95 % CI: -35.20 to -26.95), lipoprotein (a) (mean reduction: -20.44%, 95 % CI: -25.21 to -15.66), and apolipoprotein B (mean reduction: -36.32%, 95 % CI: -40.75 to -31.90) and elevated the level of high-density lipoprotein cholesterol (mean change: 6.29 %, 95 % CI: 5.12 to 7.46) and apolipoprotein A1(mean change: 4.86%, 95 % CI: 3.77 to 5.95). Therapy with and without PCSK9 antibodies did not differ in rate of adverse events (pooled rate: 50.86 % vs. 48.63%; RR: 1.03; 95 % CI: 0.92 to 1.15; P = 0.64; heterogeneity P = 0.13; I2= 40%) or serious adverse events (pooled rate: 7.14% vs. 6.74%; RR: 1.05; 95 % CI: 0.70 to 1.58; P = 0.80; heterogeneity P = 0.69; I2= 0%). PCSK9 antibody may be an effective and safe treatment for FH.
