MicroRNAs (miRNAs) are a class of ～22 nt long endogenous non-coding RNAs that play important regulatory roles in diverse organisms. Up to now, little is known about the evolutionary properties of these crucial regulators. Most miRNAs were thought to be phylogenetically conserved, but recently, a number of poorly-conserved miRNAs have been reported and miRNA innovation is shown to be an ongoing process. In this work, through the characterization of an miRNA super family, we studied the evolutionary patterns of miRNAs in vertebrates. Recently generated miRNAs seem to evolve rapidly during a certain period following their emergence. Multiple lineage-specific expansions were observed. Homolgous premiRNAs may produce mature products from the opposite stem arms following tandem duplications, which may have important contribution to miRNA innovation. Our observations of miRNAs' complicated evolutionary patterns support the notion that these key regulatory molecules may play very active roles in evolution.
WANG XiaoWo, ZHANG XueGong & LI YanDa MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST/Department of Automation, Tsinghua University, Beijing 100084, China
The Human Genome Project was launched at the end of the 1980s.Since then,the cloning and identification of functional genes has been a major focus of research across the world.In China too,the potentially profound impact of such studies on the life sciences and on human health was realized,and relevant studies were initiated in the 1990s.To advance China's involvement in the Human Genome Project,in the mid-1990s,Committee of Experts in Biology from National High Technology Research and Development Program of China(863 Program) proposed the "two 1%" goal.This goal envisaged China contributing 1% of the total sequencing work,and cloning and identifying 1% of the total human functional genes.Over the past 20 years,tremendous achievement has been accomplished by Chinese scientists.It is well known that scientists in China finished the 1% of sequencing work of the Human Genome Project,whereas,there is no comprehensive report about "whether China had finished cloning and identifying 1% of human functional genes".In the present study,the GenBank database at the National Center of Biotechnology Information,the PubMed search tool,and the patent database of the State Intellectual Property Office,China,were used to retrieve entries based on two screening standards:(i) Were the newly cloned and identified genes first reported by Chinese scientists?(ii) Were the Chinese scientists awarded the gene sequence patent? Entries were retrieved from the databases up to the cut-off date of 30 June 2011 and the obtained data were analyzed further.The results showed that 589 new human functional genes were first reported by Chinese scientists and 159 gene sequences were patented(http:gene.fudan.sh.cn/introduction/database/chinagene/chinagene.html).This study systematically summarizes China's contributions to human functional genomics research and answers the question "has China finished cloning and identifying 1% of human functional genes?" in the affirmative.
microRNAs (miRNAs) have been reported to be associated with the pathogenesis and progression of breast cancer.However,little is known about the pathways through which miRNAs regulate these processes,e.g.,the interaction between miRNAs and their target genes with regard to different pathological status of breast cancer,such as histological grades.This study investigated the possible roles of miRNAs in the differentiation of histological grades of breast cancer with a computational approach.Based on a microarray dataset,15 candidate miRNAs were identified,whose predicted target genes are enriched as differentially expressed between grade I and grade III breast tumors.Among them,9 key miRNAs focalize their target genes on 6 central signaling pathways.The SMAD7 protein,the main inhibitory protein in the TGF-β pathway,is predicted as a target of several miRNAs and is also regulated by several other pathways that are possibly targeted by miRNAs.It was hypothesized that miRNAs participate in the differentiation of breast cancer and the TGF-β pathway acts as a major implementary pathway on which several miRNAs take effect through multiple channels.The prediction power of the predicted miRNA target genes was validated on three independent datasets.The differential expression of three miRNAs was validated by real-time PCR on breast carcinoma samples of 10 patients.
AIM:To investigate the association between TP53 Arg72Pro polymorphism and esophageal cancer(EC)risk using meta-analysis. METHODS:All eligible studies published before March 1,2010 were selected by searching PubMed using keywords"p53"or"TP53","polymorphism"or"variation", "esophageal"and"cancer"or"carcinoma".Crude odds ratios(ORs)with 95%confidence intervals(CIs)were assessed for EC risk associated with TP53 Arg72Pro polymorphism using fixed-and random-effects models. RESULTS:Nine case-control studies involving 5545 subjects were included in this meta-analysis.Significantly reduced risk of EC was associated with TP53genotypes for Arg/Arg+Arg/Pro vs Pro/Pro(OR= 0.73,95%CI:0.57-0.94,P=0.014).Subgroup analyses according to the source of controls and the specimens used for determining TP53 Arg72Pro genotypes or sample size showed that significantly reduced risk was observed only in studies which have populationbased controls(Arg/Arg vs Pro/Pro:OR=0.56,95% CI:0.47-0.66,P<0.001),and use white blood cells or normal tissue to assess TP53 genotypes of cases (Arg/Arg vs Pro/Pro:OR=0.56,95%CI:0.47-0.65,P <0.001)or include at least 200 subjects(Arg/Arg vs Pro/Pro:OR=0.56,95%CI:0.47-0.65,P<0.001). Analysis restricted to well-designed studies also supported the significantly decreased risk of EC(Arg/Arg vs Pro/Pro:OR=0.54,95%CI:0.46-0.64,P<0.001). CONCLUSION:TP53 Arg72 carriers are significantly associated with decreased EC risk.Nevertheless,more welldesigned studies are needed to confirm our findings.
De-Ke Jiang Lei Yao Wen-Zhang Wang Bo Peng Wei-Hua Ren Xian-Mei Yang Long Yu
