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1.
Article in Chinese | WPRIM | ID: wpr-921527

ABSTRACT

Objective To study the stemness characteristics of uterine corpus endometrial carcinoma(UCEC)and its potential regulatory mechanism.Methods Transcriptome sequencing data of UCEC was obtained from The Cancer Genome Atlas.Gene expression profile was normalized by edgeR package in R3.5.1.A one-class logistic regression machine learning algorithm was employed to calculated the mRNA stemness index(mRNAsi)of each UCEC sample.Then,the prognostic significance of mRNAsi and candidate genes was evaluated by survminer and survival packages.The high-frequency sub-pathways mining approach(HiFreSP)was used to identify the prognosis-related sub-pathways enriched with differentially expressed genes(DEGs).Subsequently,a gene co-expression network was constructed using WGCNA package,and the key gene modules were analyzed.The clusterProfiler package was adopted to the function annotation of the modules highly correlated with mRNAsi.Finally,the Human Protein Atlas(HPA)was retrieved for immunohistochemical validation.Results The mRNAsi of UCEC samples was significantly higher than that of normal tissues(


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Endometrial Neoplasms/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Mad2 Proteins , Multigene Family , Neoplastic Stem Cells , Prognosis , Securin
2.
Article in Chinese | WPRIM | ID: wpr-888106

ABSTRACT

The longevity mechanism of ginseng(Panax ginseng) is related to its strong meristematic ability. In this paper, this study used bioinformatic methods to identify the members of the ginseng TCP gene family in the whole genome and analyzed their sequence characteristics. Then, quantitative real-time fluorescent PCR was performed to analyze the TCP genes containing elements rela-ted to meristem expression in the taproots, fibrous roots, stems, and leaves. According to the data, this study further explored the expression specificity of TCP genes in ginseng tissues, which facilitated the dissection of the longevity mechanism of ginseng. The ginseng TCP members were identified and analyzed using PlantTFDB, ExPASy, MEME, PLANTCARE, TBtools, MEGA and DNAMAN. The results demonstrated that there were 60 TCP gene family members in ginseng, and they could be divided into two classes: Class Ⅰ and Class Ⅱ, in which the Class Ⅱ possessed two subclasses: CYC-TCP and CIN-TCP. The deduced TCP proteins in ginseng had the length of 128-793 aa, the isoelectric point of 4.49-9.84 and the relative molecular mass of 14.2-89.3 kDa. They all contained the basic helix-loop-helix(bHLH) domain. There are a variety of stress response-related cis-acting elements in the promoter regions of ginseng TCP genes, and PgTCP20-PgTCP24 contained the elements associated with meristematic expression. The transcription levels of PgTCP20-PgTCP24 were high in fibrous roots and leaves, but low in stems, indicating the tissue-specific expression of ginseng TCP genes. The Class Ⅰ TCP members which contained PgTCP20-PgTCP23, may be important regulators for the growth and development of ginseng roots.


Subject(s)
Computational Biology , Gene Expression Regulation, Plant , Multigene Family , Panax/metabolism , Phylogeny , Plant Proteins/metabolism , Transcription Factors/metabolism
3.
Chinese Journal of Biotechnology ; (12): 2127-2146, 2021.
Article in Chinese | WPRIM | ID: wpr-887786

ABSTRACT

Streptomyces are major sources of bioactive natural products. Genome sequencing reveals that Streptomyces have great biosynthetic potential, with an average of 20-40 biosynthetic gene clusters each strain. However, most natural products from Streptomyces are produced in low yields under regular laboratory cultivation conditions, which hamper their further study and drug development. The production of natural products in Streptomyces is controlled by the intricate regulation mechanisms. Manipulation of the regulatory systems that govern secondary metabolite production will strongly facilitate the discovery and development of natural products of Streptomyces origin. In this review, we summarize progresses in pathway-specific regulators from Streptomyces in the last five years and highlight their role in improving the yields of corresponding natural products.


Subject(s)
Biological Products , Multigene Family , Secondary Metabolism , Streptomyces/genetics
4.
Article in English | WPRIM | ID: wpr-888782

ABSTRACT

Over-expression of the pathway specific positive regulator gene is an effective way to activate silent gene cluster. In the curret study, the SARP family regulatory gene, vasR2, was over-expressed in strain Verrucosispora sp. NS0172 and the cryptic gene cluster responsible for the biosynthesis of pentaketide ansamycin was partially activated. Two tetraketides (1 and 2) and a triketide (3) ansamycins, together with five known compounds (4-8), were isolated and elucidated from strain NS0172OEvasR2. Their NMR data were completely assigned by analysis of their HR-ESI-MS and


Subject(s)
Micromonosporaceae/metabolism , Multigene Family , Polyketides/metabolism , Rifabutin/metabolism
5.
Article in English | WPRIM | ID: wpr-881041

ABSTRACT

Constitutively expression of the pathway-specific activators is an effective method to activate silent gene clusters and improve natural product production. In this study, nine shunt products of aminoansamycins (1-9) were identified from a recombinant mutant strain S35-LAL by overexpressed the large-ATP-binding regulator of the LuxR family (LAL) gene aas1 in Streptomyces sp. S35. All the compounds showed no anti-microbial, anti-T3SS and cytotoxic activities.


Subject(s)
Biological Products/metabolism , Lactams, Macrocyclic/metabolism , Multigene Family , Organisms, Genetically Modified , Streptomyces/metabolism
6.
Article in Chinese | WPRIM | ID: wpr-828428

ABSTRACT

The WD40 transcription factor family is a gene superfamily widely found in eukaryotes, which is closely related to plant growth and development regulation. It has been reported that the WD40 transcription factor was involved in the synthesis of anthocyanins, which is one of the vital components of safflower flavonoid compounds. In this study, 40 CtWD40 members in the safflower genome were identified though bioinformatics tools and gene expression analysis methods. According to the WD40 protein sequence and phylogenetic characteristics of Arabidopsis and other plants, the safflower CtWD40 family was classified into 7 subfamilies. Conservative motif analysis was used to reveal the specific conserved motifs and gene structures of each subfamily member, and there exist a certain degree of similarities in the conserved motifs and gene structure between the closely related family members. Subsequently, the search for cis-acting elements of gene promoters found CtWD40-specific promoter elements, revealing the metabolic pathways which may involve. Next, enrichment of function analysis was employed to analyze the functional categories and cellular localization of the CtWD40 protein. Furthermore, the interactions between CtWD40 proteins predicted its potential regulatory function. Finally, 19 members of the safflower CtWD40 subfamily were analyzed by qRT-PCR, the result showed the expression patterns of these members were different in diverse tissue and flowering period. This study provides a basis for the functional and expression research of the CtWD40 genes.


Subject(s)
Carthamus tinctorius , Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Plant , Genome, Plant , Multigene Family , Phylogeny , Plant Proteins , Genetics , Transcription Factors , Genetics
7.
Article in Chinese | WPRIM | ID: wpr-828007

ABSTRACT

Glucomannan is the key active ingredient of Dendrobium catenatum, and CSLA family is responsible for glucomannan biosynthesis. In order to systematically evaluate the CSLA family members of D. catenatum, the bioinformatics methods were performed for genome-wide identification of DcCSLA gene family members through the genomic data of D. catenatum downloaded from the NCBI database, and further analyses of their phylogenetic relationship, gene structure, protein conserved domains and motifs, promoter cis-elements and gene expression profiles in response to stresses. The results showed that D. catenatum contains 13 CSLA members, all of which contain 9-10 exons. In the evolutionary relationship, CSLA genes were clustered into 5 groups, DcCSLA genes were distributed in all branches. Among which the ancestral genes of groupI existed before the monocot-dicot divergence, and groupⅡ-Ⅴ only existed in the monocot plants, indicating that group Ⅰ represents the earliest origin group. CSLA proteins are characteristic of the signature CESA_CaSu_A2 domain. Their promoter regions contain cis elements related to stresses and hormones. Under different stress treatments, low temperature induces the expression of DcCSLA5 and inhibits the expression of DcCSLA3. Infection of Sclerotium delphinii inhibits DcCSLA3/4/6/8/9/10 expression. Under the treatment of jasmonic acid, DcCSLA11 expression was significantly up-regulated, and DcCSLA2/5/7/12/13 were significantly down-regulated. These results laid a foundation for further study on the function of DcCSLA genes in glucomannan biosynthesis and accumulation.


Subject(s)
Basidiomycota , Cold Temperature , Dendrobium , Genetics , Gene Expression Regulation, Plant , Genome, Plant , Multigene Family , Phylogeny , Plant Proteins , Genetics , Stress, Physiological , Transcriptome
8.
Chinese Journal of Biotechnology ; (12): 1138-1149, 2020.
Article in Chinese | WPRIM | ID: wpr-826864

ABSTRACT

Pyrroloquinoline quinone (PQQ), an important redox enzyme cofactor, has many physiological and biochemical functions, and is widely used in food, medicine, health and agriculture industry. In this study, PQQ production by recombinant Gluconobacter oxydans was investigated. First, to reduce the by-product of acetic acid, the recombinant strain G. oxydans T1 was constructed, in which the pyruvate decarboxylase (GOX1081) was knocked out. Then the pqqABCDE gene cluster and tldD gene were fused under the control of endogenous constitutive promoter P0169, to generate the recombinant strain G. oxydans T2. Finally, the medium composition and fermentation conditions were optimized. The biomass of G. oxydans T1 and G. oxydans T2 were increased by 43.02% and 38.76% respectively, and the PQQ production was 4.82 and 20.5 times higher than that of the wild strain, respectively. Furthermore, the carbon sources and culture conditions of G. oxydans T2 were optimized, resulting in a final PQQ yield of (51.32±0.899 7 mg/L), 345.6 times higher than that of the wild strain. In all, the biomass of G. oxydans and the yield of PQQ can be effectively increased by genetic engineering.


Subject(s)
Fermentation , Gene Knockout Techniques , Gluconobacter oxydans , Genetics , Metabolism , Industrial Microbiology , Methods , Multigene Family , Genetics , Organisms, Genetically Modified , PQQ Cofactor , Genetics , Promoter Regions, Genetic , Genetics
9.
Chinese Journal of Biotechnology ; (12): 2685-2694, 2020.
Article in Chinese | WPRIM | ID: wpr-878521

ABSTRACT

Streptomyces aureofaciens DM-1 is a high-yielding 6-demethylchlortetracycline producer. The genome sequencing of DM-1 reveals a linear chromosome containing 6 824 334 bps nucleotides with GC content of 72.6%. In this genome, a total of 6 431 open reading frames were predicted by using glimmer 3.02, Genemark and Z-Curve softwares. Twenty-eight secondary metabolite biosynthetic gene clusters were uncovered by using AntiSMASH gene prediction software, including the complete 6-demethylchlortetracycline biosynthetic gene cluster. A frame-shift mutation in methyltransferase coding region was detected, which may result in the demethylation of chlortetracycline. The complete genome sequence of S. aureofaciens DM-1 provides basic information for functional genomics studies and selection of high-yielding strains for 6-demethylchlortetracycline.


Subject(s)
Base Sequence , Chlortetracycline , Demeclocycline , Multigene Family/genetics , Streptomyces aureofaciens/genetics
10.
Article in Chinese | WPRIM | ID: wpr-879492

ABSTRACT

OBJECTIVE@#To report on a case with homozygous deletion of large β gene cluster and its clinical characteristics.@*METHODS@#A total of 71 001 peripheral blood samples were subjected to capillary electrophoresis and conventional testing for common thalassemia mutations. The genotypes of suspected β gene cluster deletions were analyzed by Gap-PCR and multiplex ligation-dependent probe amplification (MLPA). Their hematological characteristics were compared by statistical analysis R software.@*RESULTS@#Eighty-nine cases were detected with Chinese @*CONCLUSION@#The carrier rate for large fragment deletions of β gene cluster in Huizhou region is rather high, for which the value of HbF is significantly increased. Attention should be paid to screening and diagnosis of rare genotype to prevent missed diagnosis and/or misdiagnosis.


Subject(s)
Gene Deletion , Homozygote , Humans , Multigene Family/genetics , Phenotype , beta-Thalassemia/genetics
11.
Article in English | WPRIM | ID: wpr-719508

ABSTRACT

BACKGROUND: Elderly asthma (EA) is increasing, but the pathogenesis is unclear. This study aimed to identify EA-related biological pathways by analyzing genome-wide gene expression profiles in sputum cells. METHODS: A total of 3,156 gene probes with significantly differential expressions between EA and healthy elderly controls were used for a hierarchical clustering of genes to identify gene clusters. Gene set enrichment analysis provided biological information, with replication from Gene Expression Omnibus expression profiles. RESULTS: Fifty-five EA patients and 10 elderly control subjects were enrolled. Two distinct gene clusters were found. Cluster 1 (n = 35) showed a lower eosinophil proportion in sputum and less severe airway obstruction compared to cluster 2 (n = 20). The replication data set also identified 2 gene clusters (clusters 1' and 2'). Among 5 gene sets significantly enriched in cluster 1 and 3 gene sets significantly enriched in cluster 2, we confirmed that 2 were significantly enriched in the replication data set (OXIDATIVE_PHOSPHORYLATION gene set in cluster 1 and EPITHELIAL MESENCHYMAL TRANSITION gene set in cluster 2'). CONCLUSIONS: The findings of 2 distinct gene clusters in EA and different biological pathways in each gene cluster suggest 2 different pathogenesis mechanisms underlying EA.


Subject(s)
Aged , Airway Obstruction , Asthma , Cluster Analysis , Dataset , Eosinophils , Epithelial-Mesenchymal Transition , Gene Expression , Humans , Multigene Family , Sputum , Transcriptome
12.
Chinese Journal of Biotechnology ; (12): 1889-1900, 2019.
Article in Chinese | WPRIM | ID: wpr-771745

ABSTRACT

Novel natural products have always been the most important sources for discovery of new drugs. Since the end of the 20th century, advances in genomics technology have contributed to decode and analyze numerous genomes, revealing remarkable potential for production of new natural products in organisms. However, this potential is hampered by laboratory culture conditions. Therefore, the integration of all these new advances is necessary to unveil these treasures, addressing the rise in resistance to antibiotics. In this review, we discuss the strategies of genome mining, inducing the expression of silent biosynthetic gene clusters and construction of biological chassis.


Subject(s)
Animals , Biological Products , Metabolism , Biosynthetic Pathways , Genetics , Genome , Genetics , Genomics , Multigene Family , Genetics
13.
Article in English | WPRIM | ID: wpr-776863

ABSTRACT

Three new phenazine-type compounds, named phenazines SA-SC (1-3), together with four new natural products (4-7), were isolated from the fermentation broth of an earwig-associated Streptomyces sp. NA04227. The structures of these compounds were determined by extensive analyses of NMR, high resolution mass spectroscopic data, as well as single-crystal X-ray diffraction measurement. Sequencing and analysis of the genome data allowed us to identify the gene cluster (spz) and propose a biosynthetic pathway for these phenazine-type compounds. Additionally, compounds 1-5 exhibited moderate inhibitory activity against acetylcholinesterase (AChE), and compound 3 showed antimicrobial activities against Micrococcus luteus.


Subject(s)
Animals , Anti-Bacterial Agents , Chemistry , Metabolism , Pharmacology , Bacterial Proteins , Genetics , Metabolism , Crystallography, X-Ray , Insecta , Microbiology , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Micrococcus luteus , Molecular Structure , Multigene Family , Phenazines , Chemistry , Metabolism , Pharmacology , Streptomyces , Chemistry , Genetics , Metabolism
14.
Article in English | WPRIM | ID: wpr-764360

ABSTRACT

BACKGROUND AND PURPOSE: Febrile seizure (FS) is a unique type of seizure that only occurs during childhood. Genelized epilepsy with febrile seizure plus (GEFS+) is a familial epilepsy syndrome associated with FS and afebrile seizure (AFS). Both seizure types are related to fever, but whether genetic susceptibility to inflammation is implicated in them is still unclear. To analyze the associations between postictal serum cytokine levels and genetic variants in the cytokine genes interleukin (IL)-1β, IL-6, and high mobility group box-1 (HMGB1) in FS and GEFS+. METHODS: Genotyping was performed in 208 subjects (57 patients with FS, 43 patients with GEFS+, and 108 controls) with the SNaPshot assay for IL-1β-31 (rs1143627), IL-1β-511 (rs16944), IL-6-572 (rs1800796), and HMGB1 3814 (rs2249825). Serum IL-1β, IL-6, and HMGB1 levels were analyzed within 2 hours after seizure attacks using the ELISA in only 68 patients (38 FS, 10 GEFS+, and 20 controls). The allele distribution, genotype distribution, and correlations with serum cytokine levels were analyzed. RESULTS: Near-complete linkage disequilibrium exists between IL-1β-31 and IL-1β-511 variants. CT genotypes of these variants were associated with significantly higher postictal serum IL-1β levels than were CC+TT genotypes in FS (both p<0.05). CT genotypes of IL-1β-31 and IL-1β-511 variants were more strongly associated with FS than were CC+TT genotypes (odds ratio=1.691 and 1.731, respectively). For GEFS+, serum IL-1β levels after AFS for CT genotypes of IL-1β-31 and IL-1β-511 were also higher than for CC+TT genotypes. No significant associations were found for IL-6 and HMGB1. CONCLUSIONS: Genetic variants located in IL-1β-31 and IL-1β-511 promotor regions are correlated with higher postictal IL-1β levels in FS. These results suggest that IL-1 gene cluster variants in IL-1β-31 and IL-1β-511 are a host genetic factor for provoking FS in Korean children.


Subject(s)
Alleles , Child , Enzyme-Linked Immunosorbent Assay , Epilepsy , Epilepsy, Generalized , Fever , Genetic Predisposition to Disease , Genotype , HMGB1 Protein , Humans , Inflammation , Interleukin-1 , Interleukin-6 , Interleukins , Linkage Disequilibrium , Multigene Family , Promoter Regions, Genetic , Seizures , Seizures, Febrile
15.
Article in Chinese | WPRIM | ID: wpr-771710

ABSTRACT

The NAC family is an important transcription factor which regulate plant growth and development, signal transduction, and stress response.In this study, the protein identification, subfamily classification, the determination of physical and chemical properties, protein structure, and expression pattern of NAC family were performed using bioinformatic methods based on the RNA-seq data of ginger. The results showed that a total of 72 NAC transcription factors were identified in 271.1 Mb total nucleotides, and they could be clustered into 13 subfamilies according to the phylogenetic tree.The physical and chemical properties, structure analysis revealed that the amino acid number and isoelectric point were different among 13 NAC subfamilies; the secondary structure of NACs transcription factors mainly consist of random coil, and the tertiary structure is similar.In addition,the expression patterns of genes under different soil moisture and Ralstonia solanacearum infection showed that 23 NACs were differentially expressed, which were mainly distributed in Ⅷ,Ⅶ, and ⅩⅤ subfamilies related to plant senescence, hormone metabolism and cell wall metabolism.The results provide some valuable information for the research and development of NAC transcription factors in ginger.


Subject(s)
Gene Expression Regulation, Plant , Ginger , Genetics , Multigene Family , Phylogeny , Plant Proteins , Genetics , Protein Structure, Tertiary , RNA, Plant , Genetics , Sequence Analysis, RNA , Transcription Factors , Genetics
16.
Article in English | WPRIM | ID: wpr-713829

ABSTRACT

BACKGROUND/OBJECTIVES: Glutathione s-transferase (GST) is involved in the formation of a multigene family comprising phase II detoxification enzymes, involved in the detoxification of reactive oxygen species. This study evaluated whether daily supplementation with kale juice could modulate levels of plasma antioxidant vitamins and oxidative stress-related parameters. We further examined whether this modulation was affected by combined GSTM1 and T1 polymorphisms. SUBJECTS/METHODS: Totally, 84 subclinical hypertensive patients having systolic blood pressure (BP) over 130 mmHg or diastolic BP over 85 mmHg, received 300 mL of kale juice daily for 6 weeks. Blood samples were drawn before start of study and after completion of 6 weeks. RESULTS: After supplementation, we observed significant decrease in DNA damage and increase in erythrocyte catalase activity in all genotypes. Plasma level of vitamin C was significantly increased in the wild/null and double null genotypes. The plasma levels of β-carotene, erythrocyte glutathione peroxidase activity, and nitric oxide were increased only in the wild/null genotype after kale juice supplementation. CONCLUSIONS: The effect of kale juice was significantly greater in the GSTM1 null genotype and wild/null genotype groups, suggesting possibility of personalized nutritional prescriptions based on personal genetics.


Subject(s)
Ascorbic Acid , Blood Pressure , Brassica , Catalase , DNA Damage , Erythrocytes , Genetics , Genotype , Glutathione Peroxidase , Glutathione Transferase , Glutathione , Humans , Hypertension , Metabolic Detoxication, Phase II , Multigene Family , Nitric Oxide , Oxidative Stress , Plasma , Prescriptions , Reactive Oxygen Species , Vitamins
17.
Article in English | WPRIM | ID: wpr-715066

ABSTRACT

OBJECTIVES: Chronic otitis media (COM) is followed by irreversible tissue damage and destruction of the middle ear structures, with the possibility of complications under the maintenance of inflammation. Inflammatory mediators such as cytokines play a crucial role in the initial stage of inflammation. The aim of this study was to evaluate the association of the polymorphisms in two innate immunity/inflammation cascade genes from interleukin-1 (IL-1) gene cluster with COM with regard to cholesteatoma. METHODS: In the cross-sectional case-control study, DNA samples were collected from 189 patients with COM and 119 controls from a population of Serbia. The +3953 C/T (rs1143634), TaqI polymorphism in interleukin-1 beta (IL-1β) gene and 86 bp variable number tandem repeat (VNTR, rs2234663) polymorphism in the IL-1 receptor antagonist (IL-1RA) gene were analyzed by polymerase chain reaction. RESULTS: The IL-1β TaqI polymorphism was not significantly different in patients compared with the control group. The significant difference between patients and controls was observed for both, genotype and allele frequencies of IL-1RA VNTR polymorphism (chi-square P < 0.01). We found that carriers of IL-1RA allele 2 (odds ratio, 0.47; 95% confidence interval, 0.29 to 0.76; P=0.004) have a favorable association with COM, using multivariate logistic analysis that included both polymorphisms, age and sex. The IL-1RA allele frequency distribution was significantly different with regard to cholesteatoma. CONCLUSION: The carriers of allele 2 of VNTR IL-1RA polymorphism had a decreased odds ratio for COM, which is in agreement with findings in other inflammatory disease and its previous association with higher IL-1RA levels. Possible down-regulation of IL-1 mediated proinflammatory signaling pathways via IL-1RA in COM as well as results of our study should be further investigated and replicated.


Subject(s)
Alleles , Case-Control Studies , Cholesteatoma , Cytokines , DNA , Down-Regulation , Ear, Middle , Gene Frequency , Genotype , Humans , Inflammation , Interleukin 1 Receptor Antagonist Protein , Interleukin-1 , Interleukin-1beta , Multigene Family , Odds Ratio , Otitis Media , Otitis , Polymerase Chain Reaction , Polymorphism, Genetic , Serbia , Tandem Repeat Sequences
18.
Braz. j. microbiol ; 48(4): 612-614, Oct.-Dec. 2017. tab
Article in English | LILACS | ID: biblio-889174

ABSTRACT

ABSTRACT Here, we show the draft genome sequence of Streptomyces sp. F1, a strain isolated from soil with great potential for secretion of hydrolytic enzymes used to deconstruct cellulosic biomass. The draft genome assembly of Streptomyces sp. strain F1 has 69 contigs with a total genome size of 8,142,296 bp and G + C 72.65%. Preliminary genome analysis identified 175 proteins as Carbohydrate-Active Enzymes, being 85 glycoside hydrolases organized in 33 distinct families. This draft genome information provides new insights on the key genes encoding hydrolytic enzymes involved in biomass deconstruction employed by soil bacteria.


Subject(s)
Bacterial Proteins/genetics , Genome, Bacterial , Glycoside Hydrolases/genetics , Soil Microbiology , Streptomyces/enzymology , Streptomyces/isolation & purification , Bacterial Proteins/metabolism , Base Composition , Brazil , Glycoside Hydrolases/metabolism , Multigene Family , Phylogeny , Streptomyces/classification , Streptomyces/genetics
20.
Article in English | WPRIM | ID: wpr-148358

ABSTRACT

PURPOSE: The microRNA-221/222 (miR-221/222) gene cluster has been reported to be associated with the promotion of epithelial-mesenchymal transition (EMT), downregulation of estrogen receptor-α, and tamoxifen resistance in breast cancer. We studied the expression of miR-222 in human breast cancer samples to analyze its relationship with clinicopathologic features of the tumor, including estrogen receptor status, expression of EMT markers, and clinical outcomes. METHODS: Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-222 in 197 invasive breast cancers. Expression of EMT markers (vimentin, smooth muscle actin, osteonectin, N-cadherin, and E-cadherin) was evaluated using immunohistochemistry. RESULTS: High miR-222 levels were associated with high T stage, high histologic grade, high Ki-67 proliferation index, and HER2 gene amplification. Its expression was significantly higher in the luminal B and human epidermal growth factor receptor 2-positive (HER2+) subtypes than in the luminal A and triple-negative subtypes. In the hormone receptor-positive subgroup, there was a significant negative correlation between miR-222 and estrogen receptor expression, and miR-222 expression was associated with EMT marker expression. In the group as a whole, high miR-222 expression was not associated with clinical outcome. However, subgroup analyses by hormone receptor status revealed that high miR-222 expression was a poor prognostic factor in the hormone receptor-positive subgroup, but not in the hormone receptor-negative subgroup. CONCLUSION: This study showed that miR-222 is associated with down-regulation of the estrogen receptor, EMT, and tumor progression in hormone receptor-positive breast cancer, indicating that miR-222 might be associated with endocrine therapy resistance and poor clinical outcome in hormone receptor-positive breast cancer.


Subject(s)
Actins , Breast Neoplasms , Breast , Cadherins , Down-Regulation , Epithelial-Mesenchymal Transition , Estrogens , Genes, erbB-2 , Humans , Immunohistochemistry , Multigene Family , Muscle, Smooth , Osteonectin , Phenobarbital , Prognosis , Real-Time Polymerase Chain Reaction , ErbB Receptors , Tamoxifen
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