Begell House Inc.
Critical Reviews™ in Eukaryotic Gene Expression
CRE
1045-4403
24
2
2014
CTLA-4 SNPs (CT60A/G, -1722T/C, -1661G/A, and -318C/T) and Systemic Lupus Erythematosus: A Meta-Analysis
89-100
10.1615/CritRevEukaryotGeneExpr.2014007884
Yun
Zhu
Department of Rheumatology and Immunology, Drum Tower Hospital, Nanjing Medical University, Nanjing, Jiangsu, PR China
Jing
Wang
Department of Hematology, Drum Tower Hospital, Nanjing, Jiangsu, PR China
Xuebing
Feng
Department of Rheumatology and Immunology, Drum Tower Hospital, Nanjing Medical University, Nanjing, Jiangsu, PR China
CTLA-4; systemic lupus erythematosus; meta-analysis; SNP; polymorphism
In this meta-analysis, we investigated the association between CTLA-4 polymorphisms (CT60A/G, -1722T/C, -1661G/A, and -318C/T) and SLE susceptibility. Data were extracted independently by two reviewers.
The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in fixed or random effects models.
Seventeen studies involving of 3931 cases and 4619 controls were identified. Significant association of promoter
-1722T/C polymorphism and SLE was observed for TT vs. CC (OR=1.63, 95% CI 1.63-2. 30, P<0.05) in the overall study population and in the Asians subgroups (OR=2. 18, 95% CI 1.70−2. 81, P<0.05); the OR for the allele T vs. C in Asians was 1.66 (95% CI 1.33−2. 07, P<0.05). For the CT60A/G polymorphism, significant association
was observed for AA vs. AG (OR=0.64, 95% CI 0.46−0.88, P<0.05) in Asians. These results suggest
that -1722T/C and CT60A/G polymorphisms in CTLA-4 are associated with SLE, particularly in Asians.
HITS-CLIP and PAR-CLIP Advance Viral MiRNA Targetome Analysis
101-116
10.1615/CritRevEukaryotGeneExpr.2014006367
Irina
Haecker
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA
Rolf
Renne
Department of Molecular Genetics and Microbiology, Shands Cancer Center, Genetics Institute, University of Florida, Gainesville, FL, USA
miRNA target
herpesvirus
EBV
KSHV
target prediction
MiRNAs regulate gene expression by binding predominantly to the 3' untranslated region (UTR) of target transcripts to prevent their translation and/or induce target degradation. In addition to the more than 1200 human miRNAs, human DNA tumor viruses such as Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) encode miRNAs. Target predictions indicate that each miRNA targets hundreds of transcripts, many of which are regulated by multiple miRNAs. Thus, target identification is a big challenge for the field. Most methods used currently investigate single miRNA−target interactions and are not able to analyze complex miRNA−target networks. To overcome these challenges, cross-linking and immunoprecipitation (CLIP), a recently developed method to study direct RNA−protein interactions in living cells, has been successfully applied to miRNA target analysis. It utilizes Argonaute (Ago)-immunoprecipitation to isolate native Ago−miRNA−mRNA complexes. In four recent publications, two variants of the CLIP method (HITS-CLIP and PAR-CLIP) were utilized to determine the targetomes of human and viral miRNAs in cells infected with the gamma-herpesviruses KSHV and EBV, which are associated with a number of human cancers. Here, we briefly introduce herpesvirus-encoded miRNAs and then focus on how CLIP technology has largely impacted our understanding of viral miRNAs in viral biology and pathogenesis.
Signal Molecule-Dependent Quorum-Sensing and Quorum-Quenching Enzymes in Bacteria
117-132
10.1615/CritRevEukaryotGeneExpr.2014008034
Yanfen
Du
Chongqing Center for Clinical Laboratory, Yuzhong, Chongqing, China; Department of Clinical Laboratory Medicine, Luzhou Medical College, Luzhou, Sichuan, China
Tian
Li
Chongqing Center for Clinical Laboratory, Yuzhong, Chongqing, China
Yafang
Wan
Chongqing Center for Clinical Laboratory, Yuzhong, Chongqing, China
Pu
Liao
Chongqing Center for Clinical Laboratory, Yuzhong, Chongqing, China
quorum sensing
autoinducers
quorum-quenching enzymes
The quick spread of nosocomial bacterial infections and the increasing prevalence of drugresistant strains make the development of novel drugs for pathogens an urgent priority. Quorum sensing (QS) is a communication mechanism used by bacteria to recognize population density fluctuations and control gene expression, which play a critical role both in intraspecies and interspecies communications and regulates microbe−host interactions. Low-molecular-weight signal compounds, such as acyl-homoserine lactone and autoinducing peptide, are used by QS to control the expression of different pathogenic factors. Thus QS−and QS signal molecules in particular−is an attractive target for developing novel antimicrobial methods. Quorum-quenching enzymes, which hydrolyze or modify signal molecules in QS circuit systems to inhibit the expression of bacteria virulence factors, have been identified both in prokaryotes and eukaryotes. Understanding the mechanism of action of quorum-quenching enzymes also provides a promising means to control bacterial infection. This review first introduces the novel principle underling signal-based QS systems in several important pathogens and then focuses on the newly identified quorum-quenching enzymes, including lactonases, acylases, oxidoreductases, and paraoxonases; this summary introduces new concepts of antimicrobial infection.
Aberrant Regulation of Alternative Pre-mRNA Splicing in Hepatocellular Carcinoma
133-149
10.1615/CritRevEukaryotGeneExpr.2014007702
Lijuan
Liu
Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan, P. R. China
Shuixiang
Xie
Department of Pathogenic Biology, Gannan Medical University, Jiangxi, P. R. China
Chuanjie
Zhang
Department of Children Health Care, Wuhan Medical Care Center for Women and Children, Wuhan, P. R. China
Fan
Zhu
Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan, P. R. China
alternative splicing
RNA processing
transcript variants
cross-talk
signaling pathway
hepatocellular carcinoma
Alternative splicing of precursors messenger RNA (pre-mRNA) is commonly used to increase the diversity of messenger RNAs expressed by the genome in normal multicellular organisms. Dysregulation of alternative splicing underlies a number of human diseases, including cancers. Increasing evidence supports the important role of this expansive layer of gene regulation in hepatocarcinogenesis. Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide because of its aggressive property and limited therapeutic options. Studies suggest that aberrant alternative splicing promotes generation of oncogenic variants in HCC, whereas tumor suppressors are self-inactivated by aberrant alternative splicing in HCC. Moreover, different spliced variants of the same gene can display distinct and even antagonistic biological functions in HCC. As a result, inhibiting the splicing of oncogenic variants and the self-inactivation of tumor suppressors are likely to be new therapy strategies. This review provides a perspective of the emerging evidence of both alternative splicing as a critical mechanism for the development of HCC and that potential cross-talk through signaling pathways among different variants might aid in the development of novel molecular targets of HCC.
SWI/SNF Chromatin Remodeling Enzymes in Melanocyte Differentiation and Melanoma
151-161
10.1615/CritRevEukaryotGeneExpr.2014007882
A.
Mehrotra
Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH
G.
Mehta
Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH
S.
Aras
Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH
A.
Trivedi
Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH
Ivana
de la Serna
Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH
melanoma
microphthalmia-associated transcription factor
SOX10
SWI/SNF chromatin remodeling enzymes
gene expression
Epidermal melanocytes are pigment-producing cells derived from the neural crest that protects skin from the damaging effects of solar radiation. Malignant melanoma, a highly aggressive cancer, arises from melanocytes.
SWI/SNF enzymes are multiprotein complexes that remodel chromatin structure and have extensive roles in cellular differentiation. Components of the complex have been found to be mutated or lost in several human cancers. This review focuses on studies that implicate SWI/SNF enzymes in melanocyte differentiation and in melanoma.
Comparative Genomics of Mycobacterium tuberculosis Drug Efflux Pumps and Their Transcriptional Regulators
163-180
10.1615/CritRevEukaryotGeneExpr.2014007826
Hong
Liu
Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, Southwest University
Jianping
Xie
Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ecoenvironments in Three Gorges Reservoir Region, Ministry of Education,
School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China
M. tuberculosis
drug efflux pumps
transcription factors
comparative genomics
Efflux pump systems are important in general drug resistance. Understanding efflux pumps can inform drug target selection and novel antibiotics designs. In this review, we have summarized the physiological roles, types, and mechanisms of drug efflux pumps. Mycobacterium tuberculosis is the causative agent of tuberculosis, a global threat to public health, and the increasing resistance of this mycobacterium to antibiotics is alarming. Therefore, we have focused on the comparative genomics of efflux pumps and relevant transcriptional regulators of M. tuberculosis.