ABSTRACT
Background: Hepatocellular carcinoma (HCC) has a high morbidity and mortality. Single nucleotide polymorphisms (SNPs) of microRNA (miRNA) may be associated with the susceptibility to develop certain malignant tumors. Aim: To study the association between SNPs of miRNA and hepatocellular carcinoma in peripheral blood samples. Material and Methods: Three SNPs in miRNA were studied in peripheral blood samples of 498 patients with HCC and 520 controls. Results: A significant association was observed between rs13299349 in miRNA3152 and HCC. AA genotype or A allele were significantly associated with increased risk of HCC. A allele was associated with the size and number of tumor foci. There was also a relationship between rs10061133 in miRNA449b and HCC. The G allele was significantly associated with increased risk of HCC compared with A allele. Conclusions: This study links rs13299349 in miRNA3152 and rs10061133 in miRNA449b with the risk of developing HCC.
Antecedentes: El carcinoma hepatocelular (CHC) tiene una alta morbilidad y mortalidad. Polimorfismos de un nucleótido (SNP) presentes en el microRNA (miRNA) circulante pueden asociarse a ciertos tumores. Objetivo: Estudiar la asociación entre la presencia de SNPs en miRNA circulante y la presencia de carcinoma hepatocelular. Material y Métodos: Se determinó la presencia de tres SNP en microRNA de sangre periférica en 498 pacientes con CHC y 520 controles. Resultados: El SNP rs13299349 en el miRNA3152 se asoció con CHC. El genotipo AA o el alelo A se asociaron con un riesgo mayor de presentar un CHC. El alelo A se asoció además con el tamaño y número de focos del tumor. Se observó también una relación entre el SNP rs10061133 en el miRNA449b y HCC. En este caso, el alelo G se relacionó con un mayor riesgo de CHC. Conclusiones: Los SNP rs13299349 en el miRNA3152 y rs10061133 en el miRNA449b se asocian al riesgo de desarrollar CHC.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Carcinoma, Hepatocellular/genetics , Polymorphism, Single Nucleotide/genetics , MicroRNAs/genetics , Genetic Association Studies/methods , Liver Neoplasms/genetics , Reference Values , Biomarkers, Tumor , Case-Control Studies , Risk Factors , Analysis of Variance , Carcinoma, Hepatocellular/pathology , Genetic Predisposition to Disease , Tumor Burden , Genotyping Techniques , Gene Frequency , Liver Neoplasms/pathologyABSTRACT
Objective To investigate the role and mechanism of RSPO1 in osteoblasts differentiation.Methods The xCELLigence system was used to study the toxicity and role of RSPO1 on the C2C12 cells proliferation.Alkaline phosphatase (ALP) activity was measured by using a phosphatase detection kit.The expression of osteoprotegerin (OPG) was determined using enzyme-linked immunosorbent assay (ELISA).Wnt/β-catenin signaling was evaluated using the TOPflash T cell factor (TCF) luciferase reporter assay.Western blotting assay was performed to confirm the accumulation of β-catenin protein.T test was used for statistical analysis.Results RSPO1 had no effect on the C2C12 cells proliferation,and it produced no toxicity to C2C12 cells.RSPO1 alone resulted in a slight increase in the activity of ALP (2.85±0.08 vs 1.74±0.21,t=3.014,P＜0.05) and the expression of OPG (1.29±0.13 vs 1.00±0.21,t=3.348,P＜0.05),whereas the combination of RSPO1 and Wnt3A significantly amplified ALP activity (81.37±5.08 vs 1.74±0.21,t=31.31,P＜0.01) and OPG protein expression (5.26±0.60 vs 1.00±0.21,t=6.99,P＜0.01).RSPO1 synergized with Wnt3A to activate TCF activity and induce accumulation of β-catenin (3.28±0.18 vs 1.00±0.21,t=10.94,P＜0.05).However,RSPO1 alone had no effect on the TCF activity and β-catenin accumulation (1.25±0.08 vs 1.00±0.21,t=2.225,P＞0.05).Conclusion Our study has revealed that RSPO1 synergized with Wnt3A in activating Wnt/β-catenin signaling pathway to induce osteoblasts differentiation,which demonstrate the therapeutic potential of RSPO1 for RA.