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
Several studies examined the impact of miR-34b/c rs4938723 polymorphism and cancer risk, but the findings are inconsistent. However, no study has been conducted to inspect the impact of miR-34b/c polymorphism on bladd...Several studies examined the impact of miR-34b/c rs4938723 polymorphism and cancer risk, but the findings are inconsistent. However, no study has been conducted to inspect the impact of miR-34b/c polymorphism on bladder cancer. This study aimed to assess possible association between rs4938723 polymorphism and bladder cancer risk.This case-control study was done on 136 pathologically proven bladder cancer patients and 144 controls. Genotyping of Pri-miR-34b/c rs4938723 polymorphism was achieved by using the polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP) method. Our findings did not show any statistically significant differences in genotype and allele frequencies between bladder cancer and controls. Larger sample sizes with diverse ethnicities are required to validate our findings.展开更多
The tumor suppressor p53 is one of the most frequently mutated genes in human cancers. MicroRNAs （miRNAs） are small non-protein coding RNAs that regulate gene expression on the post-transcriptional level. Recently, ...The tumor suppressor p53 is one of the most frequently mutated genes in human cancers. MicroRNAs （miRNAs） are small non-protein coding RNAs that regulate gene expression on the post-transcriptional level. Recently, it was shown that p53 regulates the expression of several miRNAs, thereby representing an important mechanism of p53 signaling. Several independent studies identified the members of the miR-34 family as the most prevalent p53-induced miRNAs, miR-34s are frequently silenced in variety of tumor entities, suggesting that they are important tumor suppressors. Indeed, ectopic expression of miR-34s inhibits proliferation, epithelial to mes- enchymat transition, migration, invasion, and metastasis of various cancer celt entities. Moreover, delivery or re-expression of miR-34 leads to notable repression of tumor growth and metastasis in cancer mouse models, and may therefore represent an efficient strategy for future cancer therapeutics. Besides their crucial functions in cancer, members of the miR-34 family also play important roles in spermatogenesis, stem cell differentiation, neuronal development, aging, and cardiovascular functions. Consequently, miR-34 has also been implicated in various non-cancerous diseases, such as brain disorders, osteoporosis, and cardiovascular complications.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.
基金funded by a research grant (#8067) from Zahedan University of Medical Sciences
文摘Several studies examined the impact of miR-34b/c rs4938723 polymorphism and cancer risk, but the findings are inconsistent. However, no study has been conducted to inspect the impact of miR-34b/c polymorphism on bladder cancer. This study aimed to assess possible association between rs4938723 polymorphism and bladder cancer risk.This case-control study was done on 136 pathologically proven bladder cancer patients and 144 controls. Genotyping of Pri-miR-34b/c rs4938723 polymorphism was achieved by using the polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP) method. Our findings did not show any statistically significant differences in genotype and allele frequencies between bladder cancer and controls. Larger sample sizes with diverse ethnicities are required to validate our findings.
文摘目的:评估骨髓单个核细胞中miR-34a/b/c表达水平与老年急性髓系白血病(acute myeloid leukemia,AML)患者临床特征及生存预后的关联。方法:连续纳入91例接受化疗的老年AML初治患者,同时纳入21例非血液恶性疾病患者作为对照者。采用荧光定量PCR(Quantitative real time polymerase chain reaction,qPCR)检测患者和对照者骨髓单个核细胞miR-34a/b/c的相对表达量。所有老年AML患者均根据自身疾病状况以及危险分级,选择接受常规诱导治疗方案,而后评估患者治疗反应。记录患者无事件生存期(event-free survival,EFS)及总体生存期(overall survival,OS)。结果:老年AML患者组的miR-34a和miR-34b水平显著低于对照组(P值均<0.01),而miR-34c水平在两组间无差异(P>0.05)。miR-34a高表达与无FLT3-ITD突变(P<0.05)和较低的危险分级(P<0.05)相关,miR-34b高表达与正常核型(P<0.05)、伴CEBPA双突变(P<0.01)、伴NPM1突变(P<0.05)和WBC计数≤10×109/L(P<0.05)相关,而miR-34c表达水平与患者病理特征均无关联(均P>0.05)。此外,miR-34a高表达与老年AML患者高的CR率(P<0.05)、长的EFS(P<0.01)及好的OS(P<0.01)相关,而miR-34b/c表达水平与患者的CR率、EFS及OS期均无关联(均P>0.05)。结论:miR-34a/b在老年AML患者中低表达,且它们高表达与患者良好的表现临床相关,其中miR-34a高表达还可以在一定程度上预测老年AML患者生存预后。
文摘The tumor suppressor p53 is one of the most frequently mutated genes in human cancers. MicroRNAs （miRNAs） are small non-protein coding RNAs that regulate gene expression on the post-transcriptional level. Recently, it was shown that p53 regulates the expression of several miRNAs, thereby representing an important mechanism of p53 signaling. Several independent studies identified the members of the miR-34 family as the most prevalent p53-induced miRNAs, miR-34s are frequently silenced in variety of tumor entities, suggesting that they are important tumor suppressors. Indeed, ectopic expression of miR-34s inhibits proliferation, epithelial to mes- enchymat transition, migration, invasion, and metastasis of various cancer celt entities. Moreover, delivery or re-expression of miR-34 leads to notable repression of tumor growth and metastasis in cancer mouse models, and may therefore represent an efficient strategy for future cancer therapeutics. Besides their crucial functions in cancer, members of the miR-34 family also play important roles in spermatogenesis, stem cell differentiation, neuronal development, aging, and cardiovascular functions. Consequently, miR-34 has also been implicated in various non-cancerous diseases, such as brain disorders, osteoporosis, and cardiovascular complications.
