背景:目前已有针对miRNA/mRNA轴调节骨关节炎疾病进程的分子机制研究。先前生物信息学研究发现具有临床预测价值的mRNA(磷脂酶Cδ3:phospholipase C delta 3,PLCD3)及其靶向miRNA(miR-34a-5p),尚缺实验验证其调控骨关节炎的具体作用及...背景:目前已有针对miRNA/mRNA轴调节骨关节炎疾病进程的分子机制研究。先前生物信息学研究发现具有临床预测价值的mRNA(磷脂酶Cδ3:phospholipase C delta 3,PLCD3)及其靶向miRNA(miR-34a-5p),尚缺实验验证其调控骨关节炎的具体作用及机制。目的:探讨miR-34a-5p/PLCD3轴对骨关节炎进展的调控作用及机制。方法:选择15例膝骨关节炎患者的滑膜为骨关节炎组,同时选择同期因创伤致髌骨骨折行内固定术的15例年轻患者的健康滑膜为对照组,Real-time PCR法检测滑膜中PLCD3及miR-34a-5p的表达。通过细胞转染的方法,将人滑膜关节炎成纤维细胞(human fibroblast like synovial cells-osteoarthritis,HFLS-OA)进行处理,并分为miR-34a-5p模拟物组、pCDH-PLCD3组、miR-34a-5p模拟物+pCDH-PLCD3组、miR-34a-5p抑制剂组、si-PLCD3组、miR-34a-5p抑制剂+si-PLCD3组,通过Real-time PCR法检测PLCD3和miR-34a-5p表达的关系;通过CCK-8法、细胞划痕实验检测各组HFLS-OA细胞活力及细胞迁移的影响;使用Western Blot法检测凋亡标记蛋白表达水平;使用ELISA法检测炎症因子的表达。结果与结论:①PLCD3是miR-34a-5p的直接靶标,同时PLCD3和miR-34a-5p表达水平呈负相关。②PLCD3上调会促进HFLS-OA细胞的增殖并抑制细胞迁移,而miR-34a-5p上调会显著抑制HFLS-OA细胞的活性并增强细胞迁移;miR-34a-5p过表达使HFLS-OA细胞Casp3和Casp9蛋白水平显著升高,而PLCD3过表达则表现出相反趋势。③PLCD3过表达显著增加了HFLS-OA细胞白细胞介素6和肿瘤坏死因子α的表达,而miR-34a-5p模拟物则表现出保护活性。④结果说明,miR-34a-5p/PLCD3轴可能通过调节滑膜细胞的炎症过程或凋亡来影响骨关节炎的进展。展开更多
Objective： Emerging evidence shows that microRNAs （miRNAs） function as tumor suppressors or oncogenes in human carcinogenesis. A single nucleotide polymorphism （SNP） located in the pri-miRNA promoter may affect t...Objective： Emerging evidence shows that microRNAs （miRNAs） function as tumor suppressors or oncogenes in human carcinogenesis. A single nucleotide polymorphism （SNP） located in the pri-miRNA promoter may affect the processing and expression of mature miRNA. However, previous studies showed conflicting results regarding the association of hsa-miR-34b/c rs4938723 T 〉 C promoter polymorphism with cancer. Therefore, we conducted a meta-analysis to determine the association of polymorphism with cancer risk. Methods： A computerized search of PubMed, Web of Science, and Chinese National Knowledge Infrastructure （CNKI） for publications on hsa-miR-34b/c rs4938723 T 〉 C promoter polymorphism and cancer risk was performed and the genotype data were analyzed in a meta-analysis. Odds ratios （ORs） with 95% confidence intervals （CIs） were estimated to assess the association. Test of heterogeneity, cumulative meta-analysis, sensitivity analysis and assessment of bias were performed in our meta-analysis by STATA software 12.0. Results： There was no significant association between hsa-miR-34b/c rs4938723 polymorphism and overall cancer risk in the comparison models. Moreover, subgroup analysis revealed that the variant CT （OR = 1.19, 95% CI： 1.03-1.37） and CC/CT （OR =1.18, 95% CI： 1.03-2.35） genotypes were associated with an increased risk of hepatocellular carcinoma （HCC） compared with wild-type TT genotype. However, a decreased risk of colorectal cancer （CRC） was found in the genetic model of CCFFF （OR =0.66, 95% CI： 0.47-0.92） and CC/CT-TT （OR =0.67, 95% CI： 0.49-0.93）. Conclusions： The results suggest that hsa-miR-34b/c rs4938723 polymorphism may play an opposite role in different types of cancer based on current studies, which is the main origin of heterogeneity in this metaanalysis. Further large-scale studies and functional studies between this polymorphism and cancer risk are warranted.展开更多
基金supported by National Natural Science Foundation of China (81370849, 81300472, 81070592 and 81202034)Natural Science Foundation of Jiangsu Province (BL2013032 and BK2012336)+3 种基金Nanjing City (201201053)Southeast University (3290002402)Science Foundation of Ministry of Education of China (20120092120071)the Central Universities and Graduate Innovative Fundation of Jiangsu Province (CXZZ13_0133)
文摘Objective： Emerging evidence shows that microRNAs （miRNAs） function as tumor suppressors or oncogenes in human carcinogenesis. A single nucleotide polymorphism （SNP） located in the pri-miRNA promoter may affect the processing and expression of mature miRNA. However, previous studies showed conflicting results regarding the association of hsa-miR-34b/c rs4938723 T 〉 C promoter polymorphism with cancer. Therefore, we conducted a meta-analysis to determine the association of polymorphism with cancer risk. Methods： A computerized search of PubMed, Web of Science, and Chinese National Knowledge Infrastructure （CNKI） for publications on hsa-miR-34b/c rs4938723 T 〉 C promoter polymorphism and cancer risk was performed and the genotype data were analyzed in a meta-analysis. Odds ratios （ORs） with 95% confidence intervals （CIs） were estimated to assess the association. Test of heterogeneity, cumulative meta-analysis, sensitivity analysis and assessment of bias were performed in our meta-analysis by STATA software 12.0. Results： There was no significant association between hsa-miR-34b/c rs4938723 polymorphism and overall cancer risk in the comparison models. Moreover, subgroup analysis revealed that the variant CT （OR = 1.19, 95% CI： 1.03-1.37） and CC/CT （OR =1.18, 95% CI： 1.03-2.35） genotypes were associated with an increased risk of hepatocellular carcinoma （HCC） compared with wild-type TT genotype. However, a decreased risk of colorectal cancer （CRC） was found in the genetic model of CCFFF （OR =0.66, 95% CI： 0.47-0.92） and CC/CT-TT （OR =0.67, 95% CI： 0.49-0.93）. Conclusions： The results suggest that hsa-miR-34b/c rs4938723 polymorphism may play an opposite role in different types of cancer based on current studies, which is the main origin of heterogeneity in this metaanalysis. Further large-scale studies and functional studies between this polymorphism and cancer risk are warranted.
