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1.
Genes Genomics ; 46(7): 763-774, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38733517

RESUMO

BACKGROUND: In a previous study, we found that the expression of microRNA 429 (MIR429) was decreased in dextran sodium sulfate (DSS)-induced mouse colitis tissues. OBJECTIVE: In this study, we aimed to investigate the interaction of MIR429 with TIMP metallopeptidase inhibitor 2 (TIMP2), one of its candidate target genes, in human colorectal cancer (CRC) cells and DSS-induced mouse colitis tissues. METHODS: A luciferase reporter system was used to confirm the effect of MIR429 on TIMP2 expression. The expression levels of MIR429 and target genes in cells or tissues were evaluated through quantitative RT-PCR, western blotting, or immunohistochemistry. RESULTS: We found that the expression level of MIR429 was downregulated in human CRC tissues, and also showed that TIMP2 is a direct target gene of MIR429 in CRC cell lines. Furthermore, MIR429 regulate TIMP2-mediated matrix metallopeptidases (MMPs) expression in CRC cells. We also generated cell lines stably expressing MIR429 in CRC cell lines and showed that MIR429 regulates the expression of MMPs by mediating TIMP2 expression. In addition to human CRC tissues, we found that TIMP2 was highly expressed in mouse colitis tissues and human ulcerative colitis (UC) tissues. CONCLUSIONS: Our findings suggest that the expression of endogenous MIR429 was reduced in human CRC tissues and colitis, leading to upregulation of its target gene TIMP2. The upregulation of TIMP2 by decreased MIR429 expression in CRC tissues and inflamed tissues suggests that it may affect extracellular matrix (ECM) remodeling through downregulation of MMPs. Therefore, MIR429 may have therapeutic value for human CRC and colitis.


Assuntos
Colite , MicroRNAs , Inibidor Tecidual de Metaloproteinase-2 , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Animais , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Camundongos , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Colite/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Sulfato de Dextrana , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Masculino , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Regulação para Baixo
2.
Genes Genomics ; 45(10): 1295-1304, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37523129

RESUMO

BACKGROUND: Human microRNA 452 (MIR452) has been linked to both colorectal cancer (CRC) tissues and dextran sulfate sodium (DSS)-induced colitis. OBJECTIVE: We analyzed the correlation between MIR452 and its putative target gene in human CRC cells and in mouse colitis tissues. METHODS: Luciferase reporter assay confirmed that Src homologous and collagen adaptor protein 1 (SHC1) is a direct target of MIR452. Furthermore, the expression of proteins or mRNA was assessed by immunohistochemical analysis, Western blot, or quantitative RT-PCR (qRT-PCR). RESULTS: We found that MIR452 has a potential binding site at 3'-UTR of SHC1. Likewise, MIR452 or siSHC1 transfection dramatically reduced the level of cellular SHC1 in CRC cells. The expression of SHC1 was frequently downregulated in both human CRC tissues and mouse colitis tissues. In CRC cells, we demonstrated that MIR452 regulated the expression of genes involved in the SHC1-mediated KRAS-MAPK signal transduction pathways. CONCLUSION: These findings suggest a potential defense mechanism in which MIR452 regulation of the adaptor protein SHC1 maintains cellular homeostasis during carcinogenesis or chronic inflammation. Therefore, MIR452 may have therapeutic value for human early-stage CRC and colitis.


Assuntos
Colite , Neoplasias Colorretais , MicroRNAs , Humanos , Camundongos , Animais , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais/genética , Inflamação , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/genética , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/efeitos adversos , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo
3.
J Cancer ; 14(6): 881-894, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37151391

RESUMO

MicroRNAs are endogenous, non-coding RNA that play an essential role in colorectal carcinoma (CRC) pathogenesis by targeting specific genes. This research aimed to determine and validate the target genes of the MIR133A associated with CRC. We verified that cadherin 3 (CDH3) is the direct target gene of MIR133A using a luciferase reporter assay, quantitative RT-PCR, and western blot analyses. CDH3 mRNA and protein expression were reduced significantly in CRC cells after transfection with MIR133A or siCDH3. We also verified that MIR133A regulated CDH3-mediated catenin, matrix metalloproteinase, apoptosis, and the epithelial-mesenchymal transition (EMT) pathway. Knockdown of CDH3 in CRC cell lines by siCDH3 produced similar results. Compared with adjacent non-tumor tissues, CDH3 protein expression was upregulated in CRC tissues, which is further confirmed by immunohistochemistry. Additionally, molecular and functional studies revealed that cell viability, migration, and colony formation were significantly reduced, and apoptosis was increased in CRC cell lines transfected with MIR133A or siCDH3. Our results suggest that MIR133A regulates CDH3 expression in human CRC.

4.
Am J Cancer Res ; 12(7): 3223-3241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35968353

RESUMO

The human microRNA 133A (MIR133A) was identified as a CRC-associated miRNA. It was down-regulated in human CRC tissues. We identified the putative MIR133A1 and A2 target genes by comparing the transcriptome analysis data of MIR133A1 and A2 knock-in cells with the candidate MIR133A target genes predicted by bioinformatics tools. We identified 29 and 33 putative MIR133A and A2 direct target genes, respectively. Among them, we focused on the master transcription regulator gene SRY-box transcription factor 9 (SOX9), which exhibits a pleiotropic role in cancer. We confirmed that SOX9 is a direct target gene of MIR133A by luciferase reporter assay, quantitative RT-PCR, and western blot analysis. Overexpression of MIR133A in CRC cell lines significantly decreased SOX9 and its downstream PIK3CA-AKT1-GSK3B-CTNNB1 and KRAS-BRAF-MAP2K1-MAPK1/3 pathways and increased apoptosis. Furthermore, functional studies reveal that cell proliferation, colony formation, and migration ability were significantly decreased by MIR133A-overexpressed CRC cell lines. Knockdown of SOX9 in CRC cell lines by SOX9 gene silencing showed similar results. We also used a xenograft model to show that MIR133A overexpression suppresses tumor growth and proliferation. Our results suggest that MIR133A regulates cell proliferation, migration, and apoptosis by targeting SOX9 in human colorectal cancer.

5.
Inflamm Res ; 70(8): 903-914, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34283251

RESUMO

OBJECTIVE: MicroRNAs are a class of small, non-coding RNAs that play a key role in several biological and molecular processes, including tumorigenesis. We previously identified that MIR452 is upregulated in both colorectal cancer (CRC) and colitis. However, the functional mechanisms of MIR452 and its target genes in CRC and colitis are not well understood. So, we hypothesize that MIR452 can influence CRC and DSS-induced colitis model through the regulation of IL20RA and its downstream JAK-STATs signaling pathway. METHODS: We used a luciferase reporter assay to confirm the effect of MIR452 on IL20RA expression. The protein and mRNA expression of a target gene and its associated molecules were measured by western blot, quantitative RT-PCR, and immunohistochemistry. RESULTS: We found that the IL20RA was a direct target gene of MIR452. Overexpression of MIR452 in CRC cell lines significantly decreased IL20RA and its downstream Janus kinase 1 (JAK1), Signal transducer and activator of transcription 1 (STAT1) and STAT3. Knockdown of IL20RA in CRC cell lines by IL20RA gene silencing also decreased the expression of IL20RA, JAK1, and STAT3, but not of STAT1. CONCLUSION: Our results suggest that MIR452 regulates STAT3 through the IL20RA-mediated JAK1 pathway, but not STAT1. Overall, MIR452 acts as tumor suppressor in human CRC and in a mouse colitis model. These findings suggest that MIR452 is a promising therapeutic target in the treatment of cancer and colitis.


Assuntos
Colite/metabolismo , Neoplasias Colorretais/metabolismo , Regulação da Expressão Gênica , Janus Quinase 1/metabolismo , MicroRNAs/metabolismo , Receptores de Interleucina/metabolismo , Fator de Transcrição STAT3/metabolismo , Idoso , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais
6.
Genes Genomics ; 43(1): 33-41, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33398662

RESUMO

BACKGROUND: MicroRNAs play important roles in the pathogenesis of human diseases by regulating target gene expression in specific cells or tissues. Previously, we identified microRNA 452 (MIR452), which was specifically up-regulated in early stage human colorectal cancer (CRC) tissue. OBJECTIVE: The current study aims to identify and verify the target genes of MIR452 associated with CRC. METHODS: A luciferase reporter system was used to confirm the effect of MIR452 on ASB8, NOL8, and CDR2 expression. The expression levels of MIR452 and the target genes were evaluated by quantitative RT-PCR (qRT-PCR) and western blotting. RESULTS: We verified the association between MIR452 and three genes, ASB8, NOL8, and CDR2, and showed that their transcripts were down-regulated by MIR452. Up-regulated MIR452 also down-regulated ASB8, NOL8, and CDR2 mRNA and protein levels in CRC cells. CDR2 protein expression was decreased in CRC tissues compared to adjacent non-tumor tissues. CONCLUSIONS: These results suggest that ASB8, NOL8, and CDR2 were target genes of MIR452 in CRC cells and that up-regulated MIR452 in CRC tissue regulated ASB8, NOL8, and CDR2 expression during colorectal carcinogenesis.


Assuntos
Proteínas de Transporte/genética , Neoplasias Colorretais/genética , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Idoso , Proteínas de Transporte/metabolismo , Neoplasias Colorretais/patologia , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Células Tumorais Cultivadas
7.
World J Gastroenterol ; 25(44): 6495-6507, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31802830

RESUMO

BACKGROUND: The human microRNA 375 (MIR375) is significantly downregulated in human colorectal cancer (CRC) and we have previously shown that MIR375 is a CRC-associated miRNA. The metadherin (MTDH) is a candidate target gene of MIR375. AIM: To investigate the interaction and function between MIR375 and MTDH in human CRC. METHODS: A luciferase reporter system was used to confirm the effect of MIR375 on MTDH expression. The expression levels of MIR375 and the target genes were evaluated by quantitative RT-PCR (qRT-PCR), western blotting, or immunohistochemistry. RESULTS: MTDH expression was found to be upregulated in human CRC tissues compared to that in healthy controls. We show that MIR375 regulates the expression of many genes involved in the MTDH-mediated signal transduction pathways [BRAF-MAPK and phosphatidylinositol-4,5-biphosphate-3-kinase catalytic subunit alpha (PIK3CA)-AKT] in CRC cells. Upregulated MTDH expression levels were found to inhibit NF-κB inhibitor alpha, which further upregulated NFKB1 and RELA expression in CRC cells. CONCLUSION: Our findings suggest that suppressing MIR375 expression in CRC regulates cell proliferation and angiogenesis by increasing MTDH expression. Thus, MIR375 may be of therapeutic value in treating human CRC.


Assuntos
Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , MicroRNAs/metabolismo , Proteínas de Ligação a RNA/genética , Neoplasias Retais/genética , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Colo/patologia , Neoplasias do Colo/patologia , Regulação para Baixo , Feminino , Humanos , Masculino , Neoplasias Retais/patologia , Reto/patologia , Transdução de Sinais/genética , Regulação para Cima
8.
Cancers (Basel) ; 11(10)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31652600

RESUMO

The human microRNA 452 (MIR452) was identified as a colorectal cancer (CRC)-associated micro RNA (miRNA) by miRNA expression profiling of human CRC tissues versus normal colorectal tissues. It was significantly up-regulated in human CRC tissues. However, the functional mechanisms of MIR452 and its target genes in CRC remain unclear. We identified 27 putative MIR452 target genes, and found that the vascular endothelial growth factor A (VEGFA) was a direct target gene of MIR452. Both cellular and extracellular VEGFA levels were significantly downregulated in CRC cells upon their transfection with MIR452 or siVEGFA. VEGFA expression was frequently downregulated in human CRC tissues in comparison with that in their healthy counterparts. We showed that MIR452 regulated the expression of genes in the VEGFA-mediated signal transduction pathways vascular endothelial growth factor receptor 1 (VEGFR2)-mitogen-activated protein kinase (MAPK) and VEGFR2-SRC proto-oncogene non-receptor tyrosine kinase (SRC) in CRC cells. Immunohistological analyses of xenografted MIR452-overexpressing CRC cells in mice showed that MIR452 regulated cell proliferation and angiogenesis. Furthermore, aortic ring angiogenesis assay in rats clearly showed that the number of microvessels formed was significantly reduced by MIR452 transfection. Our findings suggest that MIR452 regulates cell proliferation, cell migration, and angiogenesis by suppressing VEGFA expression in early CRC progression; therefore, MIR452 may have therapeutic value in relation to human CRC.

9.
Pathol Oncol Res ; 25(3): 953-959, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29532406

RESUMO

MiRNAs are non-coding RNAs that play important roles in the pathogenesis of human diseases by regulating target gene expression in specific cells or tissues. Previously we identified colorectal cancer (CRC) associated MIR196B, which was specifically up-regulated in CRC cells and tissue. We also identified 18 putative MIR196B target genes by comparing the mRNAs down-regulated in MIR196B-overexpressed cells with MIR196B target genes predicted by public bioinformatics tools. In this study, we verified the association between MIR196B and three genes, HOXA5, HOXB6 and GLTP. HOXA5, HOXB6 and GLTP transcripts were directly down-regulated by MIR196B. The mRNA and proteins levels of HOXA5, HOXB6 and GLTP were also down-regulated in CRC cells by the up-regulated MIR196B. GLTP protein expression was decreased in CRC tissues compared to adjacent non-tumor tissues. These results suggest that HOXA5, HOXB6, and GLTP were direct target genes of MIR196B in CRC cells, and that the up-regulated MIR196B in CRC tissue regulates the expression levels of HOXA5, HOXB6, and GLTP during colorectal carcinogenesis.


Assuntos
Proteínas de Transporte/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteínas de Homeodomínio/genética , MicroRNAs/genética , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo/genética , Humanos , Pessoa de Meia-Idade , RNA Mensageiro/genética , Regulação para Cima/genética
10.
Inflamm Res ; 67(11-12): 985-996, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30334065

RESUMO

OBJECTIVE AND DESIGN: MicroRNAs (miRNAs) play an important role in the pathogenesis of human diseases by regulating the expression of target genes in specific cells or tissues. In this study, we analyzed the association between the MIR429 and its target gene, charged multivesicular body protein 5 (CHMP5), in human colon cancer cells and in a DSS-induced colitis mouse model. MATERIALS AND METHODS: A luciferase reporter system was used to confirm the effect of MIR429 on CHMP5 expression. Protein or mRNA expression of the target gene and associated molecules were measured by Western blot or quantitative RT-PCR (qRT-PCR), respectively. Flow cytometry was used to compare cell viability or cell cycle progression. RESULTS: CHMP5 mRNA and protein expression was directly down-regulated by MIR429. We found that MIR429 inhibited colon cancer cell growth and cell cycle progression, and CHMP5 was overexpressed in the DSS-induced colitis mouse model and human ulcerative colitis (UC) tissues. CONCLUSIONS: Our findings show that CHMP5 is a direct target of MIR429 in human colon cancer cell lines and suggest that CHMP5 up-regulation as a result of reduced MIR429 expression in DSS-induced mice colitis tissues and human UC tissues may restrict apoptosis and promote cell proliferation.


Assuntos
Colite/metabolismo , Neoplasias Colorretais/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , MicroRNAs , Animais , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Colite/induzido quimicamente , Colite/genética , Colo/metabolismo , Neoplasias Colorretais/genética , Sulfato de Dextrana , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Fator de Transcrição RelA/metabolismo , Proteína Supressora de Tumor p53/metabolismo
11.
Arch Rheumatol ; 33(4): 424-430, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30874244

RESUMO

OBJECTIVES: This study aims to investigate whether bone morphogenetic protein 6 (BMP6) single-nucleotide polymorphism (SNP) is associated with susceptibility to systematic lupus erythematosus (SLE). PATIENTS AND METHODS: We analyzed the genotype and allele frequencies of BMP6 SNPs using genomic deoxyribonucleic acid isolated from 119 SLE patients (9 males, 110 females; mean age 36.4 years; range 19 to 59 years) and 509 healthy controls (323 males, 186 females; mean age 42.1 years; range 19 to 61 years). Genomic deoxyribonucleic acid was extracted from peripheral blood leukocytes using a standard phenol-chloroform method or by using a genomic deoxyribonucleic acid extraction kit. Erythrocyte sedimentation rate, C-reactive protein, and antinuclear antibody levels of SLE patients were recorded. RESULTS: Our results showed that the genotype frequencies of rs17557 and rs9505273 for BMP6 in SLE patients significantly differed from those of the control group (p=0.01 and p=0.04, respectively). The genotype frequencies of the rs17557 and rs9505273 for BMP6 in female SLE patients were also significantly different from those in female healthy controls (p=0.04 and p=0.03, respectively). We also revealed that the distribution of the main haplotypes of BMP6 SNPs in SLE patients was significantly different from their distribution in healthy controls. CONCLUSION: These results suggested that SNPs in BMP6 might be associated with susceptibility to SLE and that haplotypes of BMP6 polymorphisms might represent useful genetic markers for SLE.

12.
Int J Cancer ; 141(8): 1614-1629, 2017 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-28670764

RESUMO

MicroRNA 375 (MIR375) is significantly down regulated in human colorectal cancer (CRC) tissues; we have previously identified MIR375 as a colon cancer associated microRNA (miRNA). We identified putative MIR375 target genes by comparing the mRNA microarray analysis data of MIR375-overexpressing cells with the candidate MIR375 target genes predicted by public bioinformatic tools. We investigated that the connective tissue growth factor (CTGF) is a direct target gene of MIR375. Expression of CTGF, a ligand of epidermal growth factor receptor (EGFR), was markedly enhanced in human CRC tissues in comparison with the corresponding normal colon tissues. We demonstrated that the expression levels of molecules in EGFR signaling pathways were regulated by MIR375 in colorectal cells. Using immunohistochemistry and the xenograft of MIR375-overexpressing colorectal cells in mice, we showed that MIR375 regulates cell growth and proliferation, angiogenesis, cell migration, cell cycle arrest, apoptosis, and necrosis in colon cells. Furthermore, results of MIR375 overexpression and cetuximab treatment indicated that the apoptosis and necrosis in colon cells were synergistically enhanced. Our results suggest that the down-regulation of MIR375 modulates EGFR signaling pathways in human colorectal cells and tissues by increasing CTGF expression; therefore, MIR375 may have a therapeutic value in relation to human CRC.


Assuntos
Movimento Celular/fisiologia , Neoplasias do Colo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Receptores ErbB/metabolismo , MicroRNAs/genética , Idoso , Células CACO-2 , Estudos de Casos e Controles , Proliferação de Células/fisiologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Fator de Crescimento do Tecido Conjuntivo/genética , Receptores ErbB/genética , Feminino , Células HCT116 , Células HT29 , Humanos , Masculino , MicroRNAs/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Transdução de Sinais
13.
Mitochondrial DNA A DNA Mapp Seq Anal ; 28(1): 131-132, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27159698

RESUMO

Perilla citriodora is a diploid and an aromatic herb species belonging to the family Lamiaceae and widely distributed in East Asia. The complete chloroplast genome sequence of P. citriodora was generated by de novo assembly using whole genome next-generation sequences. The assembled chloroplast genome of P. citriodora was 152 588 bp in length and structurally divided into four distinct regions; large single copy region (83 699 bp), small single copy region (17 537 bp), and a pair of inverted repeat regions (25 676 bp). A total of 115 genes were annotated including 81 protein-coding genes, 30 tRNA genes, and four rRNA genes. Phylogenetic relationship with previously reported chloroplast genomes revealed that P. citriodora is most closely related to P. frutescens, a tetraploid Perilla species.


Assuntos
Genes de Cloroplastos , Genoma de Cloroplastos , Perilla/genética , Filogenia , Sequência de Bases , DNA de Cloroplastos , Ásia Oriental , Tamanho do Genoma , Genoma de Planta , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA
14.
J Crohns Colitis ; 10(7): 837-49, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26818658

RESUMO

BACKGROUND AND AIMS: miRNAs are non-coding RNAs that play important roles in the pathogenesis of human diseases by regulating target gene expression in specific cells or tissues. We aimed to detect miRNAs related to ulcerative colitis [UC], identify their target molecules, and analyse the correlation between the miRNAs and their target genes in colorectal cells and dextran sulphate sodium [DSS]-induced mouse colitis. METHODS: UC-associated miRNAs were identified by miRNA microarray analysis using DSS-induced colitis and normal colon tissues. The results were validated by quantitative real-time polymerase chain reaction [RT-PCR]. We identified target genes of MIR429, a colitis-associated miRNA, from our screen by comparing the mRNA microarray analysis in MIR429-overexpressed cells with predicted candidate target genes. We constructed luciferase reporter plasmids to confirm the effect of MIR429 on target gene expression. The protein expression of the target genes was measured by western blot,enzyme-linked immunosorbent assay [ELISA] analysis, or immunohistochemistry. RESULTS: We identified 37 DSS-induced colitis associated miRNAs. We investigated MIR429 that is down-regulated in DSS-induced colitis, and identified 41 target genes of MIR429. We show that the myristoylated alanine-rich protein kinase C substrate [MARCKS] is a direct target of MIR429. MARCKS mRNA and protein expression levels are down-regulated by MIR429, and MIR429 regulates the expression of MARCKS and MARCKS-mediated mucin secretion in colorectal cells and DSS-induced colitis. In addition, anti-MIR429 up-regulates MARCKS expression in colorectal cell lines. CONCLUSION: Our findings suggest that MIR429 modulates mucin secretion in human colorectal cells and mouse colitis tissues by up-regulating of MARCKS expression, thereby making MIR429 a candidate for anti-colitis therapy in human UC.


Assuntos
Colite/metabolismo , Colo/metabolismo , Regulação para Baixo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Mucinas/metabolismo , Animais , Biomarcadores/metabolismo , Western Blotting , Linhagem Celular Tumoral , Colite/induzido quimicamente , Colite/genética , Sulfato de Dextrana , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Mucinas/genética , Substrato Quinase C Rico em Alanina Miristoilada , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real
15.
J Immunol Res ; 2015: 602154, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26634217

RESUMO

Gamma-aminobutyric acid receptor subunit pi (GABRP) is involved in inhibitory synaptic transmission in the central nervous system. This gene encodes multisubunit chloride channels and is also expressed in numerous nonneuronal tissues such as the uterus and the ovaries. This study was aimed to validate whether the polymorphisms in the GABRP gene are associated with the susceptibility to systematic lupus erythematosus (SLE). The genotype frequencies of the rs929763, rs732157, and rs3805455 of the GABRP gene in SLE patients were significantly different from those of the control group (P < 0.0001, P = 0.05 and 0.002, resp.). Additional analysis showed that the genotype of the rs929763 and rs3805455 of the GABRP gene were also significantly associated with female SLE patients (P < 0.0001, P = 0.005, resp.). Two haplotype frequencies including a major haplotype of GABRP SNPs were more significantly different between the SLE patients and the healthy controls (P = 0.038 and 4.2E - 24, resp.). These results suggest that the polymorphisms in the GABRP gene might be associated with the susceptibility to SLE and the haplotype of GABRP SNPs is useful genetic marker for SLE.


Assuntos
Marcadores Genéticos/genética , Lúpus Eritematoso Sistêmico/genética , Receptores de GABA-A/genética , Adulto , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Coreia (Geográfico) , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Polimorfismo Genético , Fatores Sexuais , Transmissão Sináptica/genética
16.
Bioinformation ; 11(9): 444-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26527854

RESUMO

UNLABELLED: The National Agricultural Biotechnology Information Center (NABIC) constructed a web-based molecular marker database to provide information about 7,847 sequence-tagged site (STS) markers identified in the 11 species using a next generation sequencing (NGS) technologies. The database consists of three major functional categories: keyword search, detailed viewer and download function. The molecular marker annotation table provides detailed information such as ownership information, basic information, and STS-related characterization information. AVAILABILITY: The database is available for free at http://nabic.rda.go.kr/Molecularmarker.

17.
Oncotarget ; 6(5): 2843-55, 2015 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-25605245

RESUMO

Using miRNA microarray analysis, we identified 31 miRNAs that were significantly up-regulated or down-regulated in colon cancer tissues. We chose MIR196B, which was specifically up-regulated in colon cancer, for further study. We identified 18 putative MIR196B target genes by comparing between the mRNAs down-regulated in MIR196B-overexpressed cells and the assumed MIR196B target genes predicted by public bioinformatics tools. The association between MIR196B and FAS was verified in this study. FAS expression was constitutively elevated in normal human colorectal tissues. However, its expression was often reduced in human colorectal cancer. The decrease in FAS expression could be responsible for the reduction of apoptosis in colorectal cancer cells. In colorectal cancer tissue, we showed that MIR196B up-regulation was mutually followed by down regulation of FAS expression. We also showed that MIR196B directly repressed FAS expression in colorectal cells. Furthermore, anti-MIR196B up-regulated FAS expression and increased apoptosis in colorectal cancer cell lines. Our results suggest that the up-regulation of MIR196B modulates apoptosis in colorectal cancer cells by partially repressing FAS expression and that anti-MIR196B could be a potential candidate as an anti-cancer drug in colorectal cancer therapy.


Assuntos
Apoptose , Neoplasias Colorretais/metabolismo , MicroRNAs/metabolismo , Receptor fas/metabolismo , Idoso , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Células CACO-2 , Estudos de Casos e Controles , Caspase 3/genética , Caspase 3/metabolismo , Caspase 7/genética , Caspase 7/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Biologia Computacional , Feminino , Fluoruracila/farmacologia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Masculino , MicroRNAs/genética , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de Sinais , Transfecção , Receptor fas/genética
18.
Immunol Lett ; 156(1-2): 118-22, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24120510

RESUMO

Interferon inducible transmembrane protein (IFITM) family genes have been implicated in several cellular processes such as the homotypic cell adhesion functions of IFNs and cellular anti-proliferative activities. We previously showed that the IFITM3 single nucleotide polymorphisms (SNPs) associated with susceptibility to ulcerative colitis (UC). The present study aimed to investigate whether the polymorphisms in the IFITM1 gene are associated with susceptibility to UC. We also evaluated the expression levels in the putative functional promoter polymorphisms to determine the change of their activity. Gene expression profiles in the tissues obtained from human digestive tracts by RT-PCR, and the possible variation sites and SNPs of IFITM1 were identified by direct sequencing method. Genotype analysis in the IFITM1 SNPs was performed by high resolution melting and TaqMan probe analysis, and the haplotype frequencies of IFITM1 SNPs for multiple loci were estimated using the expectation maximization (EM) algorithm. The expression levels in the putative functional promoter polymorphisms were evaluated by performing a luciferase reporter assay. We identified two SNPs and two variation sites, g.-1920G>A (rs77537847), g.-1547delA (novel) and g.-416C>G (rs11246062) in the promoter region, and g.364delA (rs200576757) in intron 1. The genotype and allele frequencies of the g.-1920G>A polymorphism of IFITM1 gene in the UC patients were significantly different from those of the healthy controls (P=0.002 and 0.042, respectively). These results suggest that the g.-1920G>A polymorphism in IFITM1 may be associated with susceptibility to UC.


Assuntos
Antígenos de Diferenciação/genética , Colite Ulcerativa/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático/genética , Colite Ulcerativa/etnologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Haplótipos , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , República da Coreia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Análise de Sequência de DNA
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