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Braz. dent. j ; 32(4): 74-82, July-Aug. 2021. tab, graf
Article in English | LILACS, BBO | ID: biblio-1345513


Abstract The Inhibitor of Growth (ING) gene family is a group of tumor suppressor genes that play important roles in cell cycle control, senescence, DNA repair, cell proliferation, and apoptosis. However, inactivation and downregulation of these proteins have been related in some neoplasms. The present study aimed to evaluate the immunohistochemical profiles of ING3 and ING4 proteins in a series of benign epithelial odontogenic lesions. Methods: The sample comprised of 20 odontogenic keratocysts (OKC), 20 ameloblastomas (AM), and 15 adenomatoid odontogenic tumors (AOT) specimens. Nuclear and cytoplasmic immunolabeling of ING3 and ING4 were semi-quantitatively evaluated in epithelial cells of the odontogenic lesions, according to the percentage of immunolabelled cells in each case. Descriptive and statistics analysis were computed, and the p-value was set at 0.05. Results: No statistically significant differences were found in cytoplasmic and nuclear ING3 immunolabeling among the studied lesions. In contrast, AOTs presented higher cytoplasmic and nuclear ING4 labeling compared to AMs (cytoplasmic p-value = 0.01; nuclear p-value < 0.001) and OKCs (nuclear p-value = 0.007). Conclusion: ING3 and ING4 protein downregulation may play an important role in the initiation and progression of more aggressive odontogenic lesions, such as AMs and OKCs.

Resumo Objetivos: A família dos Genes Inibidores de Crescimento (ING) é um grupo de genes supressores tumorais que desempenham papéis importantes no controle do ciclo celular, na senescência, no reparo do DNA, na proliferação celular e na apoptose. No entanto, a inativação e a regulação negativa dessas proteínas têm sido relacionadas em algumas neoplasias. O objetivo do presente estudo foi avaliar o perfil imuno-histoquímico das proteínas ING3 e ING4 em uma série de lesões odontogênicas epiteliais benignas. Métodos: A amostra foi composta por espécimes de 20 ceratocistos odontogênicos (CO), 20 ameloblastomas (AM) e 15 tumores odontogênicos adenomatoides (TOA). A imunoexpressão nuclear e citoplasmática de ING3 e ING4 foram avaliadas semi-quantitativamente nas células epiteliais das lesões odontogênicas, de acordo com a porcentagem de células imunomarcadas em cada caso. As análises descritivas e estatísticas foram computadas, e o valor de p estabelecido foi de 0,05. Resultados: Não foram encontradas diferenças estatisticamente significativas na imunoexpressão citoplasmática e nuclear de ING3 entre as lesões estudadas. Em contrapartida, os TOAs apresentaram maior marcação citoplasmática e nuclear de ING4 em comparação aos AMs (valor de p citoplasmático=0,01; valor de p nuclear <0,001) e COs (valor nuclear de p=0,007). Conclusão: A regulação negativa das proteínas ING3 e ING4 pode desempenhar um papel importante na iniciação e na progressão de lesões odontogênicas mais agressivas, como AMs e COs.

Humans , Ameloblastoma , Odontogenic Cysts , Odontogenic Tumors , Homeodomain Proteins , Cell Cycle Proteins , Tumor Suppressor Proteins , Cell Proliferation
Article in Chinese | WPRIM | ID: wpr-879542


OBJECTIVE@#To explore the genetic etiology for a newborn with corneal opacity.@*METHODS@#The neonate and her parents were subjected to routine G-banding chromosomal karyotyping analysis. Copy number variation (CNV) was analyzed with low-coverage whole-genome sequencing (WGS) and single nucleotide polymorphism microarray (SNP array).@*RESULTS@#No karyotypic abnormality was found in the newborn and her parents. Low-coverage WGS has identified a de novo 5.5 Mb microdeletion at chromosome 8q21.11-q21.13 in the neonate, which encompassed the ZFHX4 and PEX2 genes. The result was confirmed by SNP array-based CNV analysis.@*CONCLUSION@#The newborn was diagnosed with chromosome 8q21.11 deletion syndrome. ZFHX4 may be one of the key genes underlying this syndrome.

Chromosome Banding , Chromosomes, Human, Pair 8/genetics , DNA Copy Number Variations , Female , Genetic Testing , Homeodomain Proteins/genetics , Humans , Infant, Newborn , Karyotyping , Monosomy/genetics , Peroxisomal Biogenesis Factor 2/genetics , Polymorphism, Single Nucleotide , Transcription Factors/genetics
Article in Chinese | WPRIM | ID: wpr-879523


OBJECTIVE@#To analyze the clinical and genetic characteristics of a patient with congenital isolated adrenocorticotropic hormone deficiency (IAD).@*METHODS@#Clinical characteristics of the patient was reviewed. Genomic DNA of the child was subjected to whole exome sequencing.@*RESULTS@#Genetic testing has confirmed the diagnosis of congenital IAD by identification of compound heterozygous variants of the TBX19 gene, which included a pathogenic nonsense c.535C>T (p.R179X) variant inherited from his father and a novel missense c.298C>T (p.R100C) variant inherited from his mother.@*CONCLUSION@#Congenital IAD due to variants of the TBX19 gene is a rare autosomal recessive disease. It is characterized by low plasma adrenocorticotropic hormone and cortisol levels but normal levels of other pituitary hormones. Delayed diagnosis may lead to severe early-onset adrenal failure and wrong treatment which may result in neonatal mortality. Hydrocortisone replacement is effective. Detection of pathogenic variant of TBX19 gene is the key to diagnosis.

Adrenal Insufficiency/genetics , Child , Homeodomain Proteins/genetics , Humans , T-Box Domain Proteins/genetics
Journal of Experimental Hematology ; (6): 1085-1092, 2021.
Article in Chinese | WPRIM | ID: wpr-888522


OBJECTIVE@#To investigate the effect and molecular mechanism of miR-142-3p to the proliferation, cycle and apoptosis of acute B lymphocytic leukemia (B-ALL) cells by regulating the homeobox gene 5 (HOXA5) expression.@*METHODS@#Real-time fluorescence quantitative PCR was used to detect the expression levels of miR-142-3p and HOXA5 in human B-ALL cell Nalm6 cell line and human B lymphoblast Hmy2-cir cells. Nalm6 was transfected by using liposome transfection technology, miR-142-3p mimic, pcDNA-HOXA5 overexpression plasmid, miR-142-3p mimic+pcDNA-HOXA5 overexpression plasmid, and control. The binding site of HOXA5 and miR-142-3p was predicted according to, and the targeting relationship between miR-142-3p and HOXA5 gene was detected by double luciferase reporter gene experiment. The effect of miR-142-3p to the proliferation of Nalm6 cells was detected using the Cell Counting Box-8 (CCK-8) method and cell clone formation experiments. Flow cytometry was used to detect the effects of miR-142-3p to cell cycle distribution and apoptosis of Nalm6 cells. The expression levels of cell cycle-related proteins, including G@*RESULTS@#Compared with Hmy2-cir cells, miR-142-3p showed low expression in Nalm6 cells and HOXA5 showed high expression (P<0.05). MiR-142-3p and HOXA5 3'-UTR showed complementary binding regions, the luciferase activity of miR-142-3p mimic and wild-type HOXA5 3'-UTR was significantly lower than that of miR-142-3p negative control and wild-type HOXA5 3'-UTR (P<0.05). The proliferation of Nalm6 cells and the number of cell clones could be inhibited by miR-142-3p mimic after 48 and 72 hours of transfection (P<0.05), which causing G@*CONCLUSION@#MiR-142-3p can inhibit the proliferation of Nalm6 cells by targeting down-regulation the expression of HOXA5, arrest the G

Apoptosis , Cell Line, Tumor , Cell Proliferation , Genes, Homeobox , Homeodomain Proteins/genetics , Humans , Leukemia, B-Cell/genetics , MicroRNAs/genetics
Chinese Medical Journal ; (24): 2340-2352, 2021.
Article in English | WPRIM | ID: wpr-921125


BACKGROUND@#Emerging evidence indicates that the sineoculis homeobox homolog 1-eyes absent homolog 1 (SIX1-EYA1) transcriptional complex significantly contributes to the pathogenesis of multiple cancers by mediating the expression of genes involved in different biological processes, such as cell-cycle progression and metastasis. However, the roles of the SIX1-EYA1 transcriptional complex and its targets in colorectal cancer (CRC) are still being investigated. This study aimed to investigate the roles of SIX1-EYA1 in the pathogenesis of CRC, to screen inhibitors disrupting the SIX1-EYA1 interaction and to evaluate the efficiency of small molecules in the inhibition of CRC cell growth.@*METHODS@#Real-time quantitative polymerase chain reaction and western blotting were performed to examine gene and protein levels in CRC cells and clinical tissues (collected from CRC patients who underwent surgery in the Department of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, between 2016 and 2018, n = 24). In vivo immunoprecipitation and in vitro pulldown assays were carried out to determine SIX1-EYA1 interaction. Cell proliferation, cell survival, and cell invasion were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clonogenic assay, and Boyden chamber assay, respectively. The Amplified Luminescent Proximity Homogeneous Assay Screen (AlphaScreen) method was used to obtain small molecules that specifically disrupted SIX1-EYA1 interaction. CRC cells harboring different levels of SIX1/EYA1 were injected into nude mice to establish tumor xenografts, and small molecules were also injected into mice to evaluate their efficiency to inhibit tumor growth.@*RESULTS@#Both SIX1 and EYA1 were overexpressed in CRC cancerous tissues (for SIX1, 7.47 ± 3.54 vs.1.88 ± 0.35, t = 4.92, P = 0.008; for EYA1, 7.61 ± 2.03 vs. 2.22 ± 0.45, t = 6.73, P = 0.005). The SIX1/EYA1 complex could mediate the expression of two important genes including cyclin A1 (CCNA1) and transforming growth factor beta 1 (TGFB1) by binding to the myocyte enhancer factor 3 consensus. Knockdown of both SIX1 and EYA1 could decrease cell proliferation, cell invasion, tumor growth, and in vivo tumor growth (all P < 0.01). Two small molecules, NSC0191 and NSC0933, were obtained using AlphaScreen and they could significantly inhibit the SIX1-EYA1 interaction with a half-maximal inhibitory concentration (IC50) of 12.60 ± 1.15 μmol/L and 83.43 ± 7.24 μmol/L, respectively. Administration of these two compounds could significantly repress the expression of CCNA1 and TGFB1 and inhibit the growth of CRC cells in vitro and in vivo.@*CONCLUSIONS@#Overexpression of the SIX1/EYA1 complex transactivated the expression of CCNA1 and TGFB1, causing the pathogenesis of CRC. Pharmacological inhibition of the SIX1-EYA1 interaction with NSC0191 and NSC0933 significantly inhibited CRC cell growth by affecting cell-cycle progression and metastasis.

Animals , Cell Line, Tumor , Cell Proliferation , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Genes, Homeobox , Homeodomain Proteins/metabolism , Humans , Intracellular Signaling Peptides and Proteins , Mice , Mice, Nude , Nuclear Proteins/genetics , Protein Tyrosine Phosphatases/genetics
Braz. j. med. biol. res ; 54(9): e10931, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249340


Tobacco can induce reactive oxygen species (ROS) production extensively in cells, which is a major risk factor for oral leukoplakia (OLK) development. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, upregulated in a variety of malignant tumors. We previously found that nicotine, the main ingredient of tobacco, promotes oral carcinogenesis via regulating Prx1. The aim of the present study was to screen and identify the Prx1 interacting proteins and investigate the mechanisms of nicotine on the development of OLK. Through liquid chromatography-tandem mass spectrometry combined with bioinformatics analysis, the candidate Prx1 interacting proteins of cofilin-1 (CFL1), tropomyosin alpha-3 chain (TPM3), and serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A) were screened in human dysplastic oral keratinocyte cells treated with nicotine. CFL1, TPM3, and PPP2R1A were highly expressed in human OLK tissues. The expression of CFL1 increased and the expression of PPP2R1A decreased in OLK of smokers compared to that in OLK of non-smokers. Nicotine upregulated CFL1 and downregulated PPP2R1A in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK tissues in mice in part dependent on Prx1. Furthermore, the in-situ interaction of CFL1, TPM3, and PPP2R1A with Prx1 were validated in human OLK tissues. Our results suggested that tobacco might promote the development of OLK via regulating Prx1 and its interacting proteins CFL1 and PPP2R1A.

Animals , Mice , Leukoplakia, Oral/chemically induced , Peroxiredoxins/metabolism , Nicotine , Carrier Proteins , Homeodomain Proteins , Carcinogenesis
Article in Chinese | WPRIM | ID: wpr-879790


OBJECTIVE@#To study the clinical significance of minimal residual disease (MRD) in B-lineage acute lymphoblastic leukemia (B-ALL) pediatric patients with different fusion gene backgrounds.@*METHODS@#A retrospective analysis was performed on the medical data of 441 B-ALL children who were treated from January 2008 to April 2015. Among the 441 children, 336 had negative fusion gene, 79 had positive @*RESULTS@#In patients with negative fusion gene, the positive MRD group had significantly lower overall survival (OS) rate and event-free survival (EFS) rate (@*CONCLUSIONS@#MRD has the most definite prognostic significance in pediatric B-ALL patients with negative fusion gene, while it has unsatisfactory prognostic significance in those with positive

Child , Core Binding Factor Alpha 2 Subunit , Disease-Free Survival , Homeodomain Proteins , Humans , Neoplasm, Residual/genetics , Oncogene Proteins, Fusion/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis , Retrospective Studies
Arch. endocrinol. metab. (Online) ; 63(2): 167-174, Mar.-Apr. 2019. tab, graf
Article in English | LILACS | ID: biblio-1001214


ABSTRACT The first description of patients with combined pituitary hormone deficiencies (CPHD) caused by PROP1 mutations was made 20 years ago. Here we updated the clinical and genetic characteristics of patients with PROP1 mutations and summarized the phenotypes of 14 patients with 7 different pathogenic PROP1 mutations followed at the Hospital das Clínicas of the University of Sao Paulo. In addition to deficiencies in GH, TSH, PRL and gonadotropins some patients develop late ACTH deficiency. Therefore, patients with PROP1 mutations require permanent surveillance. On magnetic resonance imaging, the pituitary stalk is normal, and the posterior lobe is in the normal position. The anterior lobe in patients with PROP1 mutations is usually hypoplastic but may be normal or even enlarged. Bi-allelic PROP1 mutations are currently the most frequently recognized genetic cause of CPHD worldwide. PROP1 defects occur more frequently among offspring of consanguineous parents and familial cases, but they also occur in sporadic cases, especially in countries in which the prevalence of PROP1 mutations is relatively high. We classified all reported PROP1 variants described to date according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines: 29 were pathogenic, 2 were likely pathogenic, and 2 were of unknown significance. An expansion of the phenotype of patients with PROP1 mutations was observed since the first description 20 years ago: variable anterior pituitary size, different pathogenic mutations, and late development of ACTH deficiency. PROP1 mutations are the most common cause of autosomal recessive CPHD with a topic posterior pituitary lobe. Arch Endocrinol Metab. 2019;63(2):167-74

Humans , Male , Female , Homeodomain Proteins/genetics , Mutation/genetics , Phenotype , Septo-Optic Dysplasia/genetics , Hypopituitarism/genetics
Article in Chinese | WPRIM | ID: wpr-774050


Mowat-Wilson syndrome (MWS) is a rare autosomal dominant genetic disease caused by zinc finger E-box-binding homeobox 2 (ZEB2) gene mutation and has various clinical manifestations including intellectual disability/global developmental delay, unusual facies and multiple congenital malformations. This article reports the clinical features and gene mutations of three children diagnosed with MWS by ZEB2 gene analysis. All three children had Hirschsprung disease and unusual facies. One child died of severe heart failure and pneumonia at the age of 4 months. Global developmental delay was not discovered by her parents due to her young age. The other two children had severe global developmental delay. All three children carried a de novo heterozygous nonsense mutation in the ZEB2 gene, among which c.756C>A (p.Y252X) had not been reported before. Such mutations produced truncated proteins and were highly pathogenic. MWS is presented with strong clinical and genetic heterogeneity. Clinicians should consider the possibility of MWS when a child has unusual facies of MWS, intellectual disability/global developmental delay and multiple congenital malformations. Gene detection helps to make a confirmed diagnosis.

Facies , Female , Hirschsprung Disease , Homeodomain Proteins , Humans , Intellectual Disability , Microcephaly , Repressor Proteins
Article in Chinese | WPRIM | ID: wpr-773512


OBJECTIVE@#To investigate the role of zinc-fingers and homeoboxes 2 (ZHX2) in regulating μ-opioid receptor expression in the dorsal root ganglion (DRG) in mice with peripheral nerve injury-induced pain hypersensitivity.@*METHODS@#Forty-eight male adult C57BL6J mice were randomized into 4 groups and subjected to chronic constriction injury (CCI) of the sciatic nerve or sham operation followed by microinjection of a specific small interfering RNA (siRNA) of ZHX2 or a negative control siRNA sequence (siNC) into the DRG. Seven days later, the mice were examined for changes in the hind paw withdrawal frequency (PWF), after which the DRG tissue was collected for detecting the expressions of μ-opioid receptor at the mRNA and protein levels using RT-qPCR and Western blotting. In another experiment, the DRG tissues were collected from 6 mice (21-day-old) for primary culture of the DRG neurons, which were transfected with ZHX2 siRNA or the siNC to observe the changes in the expressions of ZHX2 and μ-pioid receptor.@*RESULTS@#Microinjection of ZHX2 siRNA into the ipsilateral L3 and L4 DRGs significantly reversed CCI-induced μ-pioid receptor downregulation in the injured DRG and alleviated CCI-induced mechanical allodynia in the mice. In the cell experiment, ZHX2 knockdown obviously upregulated the mRNA and protein expressions of opioid receptor in the primary cultured DRG neurons.@*CONCLUSIONS@#ZHX2 knockdown in the DRG reverses CCI-induced down-regulation of μ opioid receptor to alleviate periphery nerve injury-induced pain hypersensitivity in mice.

Animals , Ganglia, Spinal , Homeodomain Proteins , Hyperalgesia , Male , Mice , Neuralgia , Rats, Sprague-Dawley , Receptors, Opioid, mu
Article in Chinese | WPRIM | ID: wpr-775986


Objective To detect the methylation status of SALL3 gene promoter region in normal cervical tissues,cervical cancer tissues,and cervical cancer cell lines and thus explore the relationship between methylation status and the expression of SALL3 gene.Methods The DNA methylation statuses of SALL3 gene in normal cervical,cervical cancer tissues and cervical cancer cell lines were analyzed by methylation-specific PCR(MS-PCR).The expressions of SALL3 mRNA in cervical cancer cell lines,cervical cancer tissues,and normal cervical tissues were detected by RT-PCR.Results In cervical cancer and matched peri-carcinomatous samples,the methylation levels of SALL3 were up-regulated(CCa .CCap:=0.046;CCa .NC =0.039)and the protein expressions were down-regulated(CCa .CCap:=0.012;CCa .NC =0.000)when compared with normal cervix samples.The mRNA levels of SALL3 in HeLa and SiHa cells treated with 5-Azacytidine were elevated in a dose-dependent manner(HeLa:=0.001;SiHa:=0.002).The methylation level of SALL3 was higher in high risk human papillomavirus(HPV)-positive cervical samples than in HPV-negative cervical samples(=0.014),which also resulted in a descending SALL3 expression in HPV-positive samples(=0.021).Conclusions The hypermethylation of SALL3 in promoter regions inhibits the expression of SALL3 in cervical cancer tissue samples.Infection with high-risk HPV serotypes may increase the methylation of SALL3 promoter region,silence its expression,and thus promote the development of cervical cancer.

Cell Line, Tumor , DNA Methylation , Female , Gene Expression Regulation, Neoplastic , HeLa Cells , Homeodomain Proteins , Genetics , Humans , Papillomavirus Infections , Genetics , Promoter Regions, Genetic , RNA, Messenger , Genetics , Transcription Factors , Genetics , Uterine Cervical Neoplasms , Genetics
Article in English | WPRIM | ID: wpr-772271


Genetic studies have revealed a critical role of Distal-homeobox (Dlx) genes in bone formation, and our previous study showed that Dlx2 overexpressing in neural crest cells leads to profound abnormalities of the craniofacial tissues. The aim of this study was to investigate the role and the underlying molecular mechanisms of Dlx2 in osteogenic differentiation of mouse bone marrow stromal cells (BMSCs) and pre-osteoblast MC3T3-E1 cells. Initially, we observed upregulation of Dlx2 during the early osteogenesis in BMSCs and MC3T3-E1 cells. Moreover, Dlx2 overexpression enhanced alkaline phosphatase (ALP) activity and extracellular matrix mineralization in BMSCs and MC3T3-E1 cell line. In addition, micro-CT of implanted tissues in nude mice confirmed that Dlx2 overexpression in BMSCs promoted bone formation in vivo. Unexpectedly, Dlx2 overexpression had little impact on the expression level of the pivotal osteogenic transcription factors Runx2, Dlx5, Msx2, and Osterix, but led to upregulation of Alp and Osteocalcin (OCN), both of which play critical roles in promoting osteoblast maturation. Importantly, luciferase analysis showed that Dlx2 overexpression stimulated both OCN and Alp promoter activity. Through chromatin-immunoprecipitation assay and site-directed mutagenesis analysis, we provide molecular evidence that Dlx2 transactivates OCN and Alp expression by directly binding to the Dlx2-response cis-acting elements in the promoter of the two genes. Based on these findings, we demonstrate that Dlx2 overexpression enhances osteogenic differentiation in vitro and accelerates bone formation in vivo via direct upregulation of the OCN and Alp gene, suggesting that Dlx2 plays a crucial role in osteogenic differentiation and bone formation.

Animals , Cell Differentiation , Physiology , Core Binding Factor Alpha 1 Subunit , Homeodomain Proteins , Metabolism , Mesenchymal Stem Cells , Metabolism , Mice , Mice, Nude , Osteoblasts , Metabolism , Osteocalcin , Osteogenesis , Physiology , Transcription Factors , Metabolism , Up-Regulation
Article in Chinese | WPRIM | ID: wpr-771906


OBJECTIVE@#To explore the clinical features and therapeutic efficacy in adult ALL patients with t (1; 19) (E2A-PBX1).@*METHODS@#The clinic data of 19 adult ALL patients with t (1; 19) (E2A-PBX1) in our hospital from Nov. 22, 2010 to Apr. 4, 2018 were collected. The clinical features,complete remission (CR) rate, overall survival (OS) rate and relapse-free survival (RFS) rate of patients received chemotherapy and chemotherapy+HSCT were analyzed.@*RESULTS@#In all the 19 patients, the median age was 24 (14-66), median WBC count was 16.47×109 (1.8-170.34)/L, median Hb level was 98 (65-176) g/L, median Plt count was 50 (15-254)×109/L. Pre B-ALL were 17 cases (89.5%), and common B-ALL were 2 cases (10.5%). Patients received the induction therapy, the overall CR rate was 94.7%, one course CR rate was 94.7%, 4 year OS rate was 47.1% and RFS rate was 43.3%. The OS rate and RFS rate of patients received transplantation were slightly higher than those of patients not received transplantation (OS: 62.5% vs 36.7%) (P=0.188);RFS (62.5% vs 38.9%) (P=0.166).@*CONCLUSION@#Most adult ALL patients with t (1; 19) (E2A-PBX1) is Pre B-ALL by Immunophenotyping, as compared with the pediatric patients, the therapeutic efficacy for adult patients with t (1; 19) (E2A-PBX1) is worsen, therefore, stem cell transplantation is still acquired for better long term survival.

Adult , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 19 , Homeodomain Proteins , Genetics , Humans , Immunophenotyping , Oncogene Proteins, Fusion , Genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Genetics , Therapeutics , Recurrence , Remission Induction
Article in Chinese | WPRIM | ID: wpr-771892


OBJECTIVE@#RAG1 plays important roles in lymphopoiesis and immune system, its dysfunction may result in the malignancies of hemopoietic system. The aim of this study was to investigate the characteristics of RAG1 expression in adult B-cell acute lymphoblastic leukemia (B-ALL), and to analyze the clinical significances.@*METHODS@#Quantitative PCR (q-PCR) was performed to evaluate the expression of RAG1 in 104 newly diagnosed, 22 relapsed adult B-ALL patients and 30 normal controls, the clinical significances of RAG1 expression were analyzed.@*RESULTS@#Compared with normal controls, newly diagnosed and relapsed adult B-ALL patients showed higher RAG1 expression level (3.94 vs 1.23) (P<0.01), (5.86 vs 1.23) (P<0.01). The analysis of paired simples from 6 cases of newly diagnosed and relapsed B-ALL showed that the expression level of RAG1 at relapse was significantly higher than that at new diagnosis (13.65 vs 2.31) (P<0.01). The RAG1 expression level in IK6 positive patients was higher than that in IK6 negative patients (5.30 vs 2.11) (P<0.05). The ratio of patients with LDH>1 000 U/L in RAG1 high expression group was higher than that in RAG1 low expression group (42.2% vs 20.5%) (P<0.05).@*CONCLUSION@#RAG1 up-regulation may play an important role in the development of adult B-ALL especially when relapsed, which may also take part in the formation of Ik6. Monitoring RAG1 expression may provide a new method to evaluate the prognosis of adult B-ALL patients.

Acute Disease , Adult , B-Lymphocytes , Homeodomain Proteins , Genetics , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Genetics , Prognosis
Article in Chinese | WPRIM | ID: wpr-777523


A stable hepatoma cell line(Hep G2 cell) insulin resistance model was established and used to analyze the effect of effective components of Mori Folium in alleviating insulin resistance,and preliminary explore the mechanism for alleviating insulin resistance. The Hep G2 insulin action concentration and the duration of action were investigated using the glucose oxidase method(GOD-POD method) to establish a stable Hep G2 insulin resistance model. Normal control group,model group,Mori Folium polysaccharide group,Mori Folium flavonoid group and rosiglitazone group were divided to determine the glucose consumption. The effect of Mori Folium effective components on Hep G2 insulin resistance was analyzed. The mRNA expressions of JNK,IRS-1 and PDX-1 in each group were detected by Real-time quantitative PCR(qRT-PCR). The protein expressions of p-JNK,IRS-1 and PDX-1 were detected by Western blot. And the mechanism of effective components of Mori Folium in alleviating insulin resistance was investigated. The results showed that the glucose consumption was significantly decreased in the insulin resistance cells after incubation with 25. 0 mg·L-1 insulin for 36 h(P<0. 01),and the model was relatively stable within 36 h. Mori Folium polysaccharides and flavonoids all alleviated insulin resistance,among which Mori Folium flavonoids had better effect in alleviating Hep G2 insulin resistance(P<0. 05). The qRT-PCR analysis showed that Mori Folium polysaccharides and flavonoids could inhibit JNK and IRS-1 mRNA expressions,while enhancing PDX-1 mRNA expression. Western blot analysis displayed that Mori Folium polysaccharides and flavonoids could inhibit p-JNK and IRS-1 protein expressions,while enhancing PDX-1 protein expression. Mori Folium polysaccharides and flavonoids can alleviate insulin resistance in Hep G2 cells,and its mechanism may be the alleviation of insulin resistance by inhibiting JNK signaling pathway.

Drugs, Chinese Herbal , Pharmacology , Glucose , Hep G2 Cells , Homeodomain Proteins , Metabolism , Humans , Insulin , Insulin Receptor Substrate Proteins , Metabolism , Insulin Resistance , MAP Kinase Kinase 4 , Metabolism , MAP Kinase Signaling System , Morus , Chemistry , Plant Leaves , Chemistry , Trans-Activators , Metabolism
Int. j. morphol ; 36(3): 991-996, Sept. 2018. graf
Article in English | LILACS | ID: biblio-954220


The failure of fusion of nasal and maxillary processes results in cleft lip and palate (CLP), which is one of the most common birth defects. The morphopathogenesis of this pathology is multifactorial and still largely unclear. The aim of this study was to evaluate the presence of nestin, transcriptor factor SOX3 (Sox3) and homeobox protein DLX-4 (Dlx-4) in complete unilateral (CU) and complete bilateral (CB) CLP affected facial tissue. Oral mucosa tissue samples were obtained from 17 CUCLP and 13 CBCLP patients during surgical cleft correction and 6 unaffected control subjects. Obtained tissue sections were stained with hematoxylin and eosin and by immunohistochemistry for nestin, Sox3 and Dlx-4. The intensity of staining was graded semiquantitatively. Nestin-positive structures were detected in all CUCLP and CBCLP patients' tissue samples, varying from moderate number of nestin-positive structures to numerous. Sox3 immunoreactivity was more prominent in epithelial cells in both patient groups with frequently patchy distribution. Mainly moderate number of Dlx-4-positive cells was observed in most of tissue samples. Statistically significant moderate positive correlation was found between nestin and Sox3 factors in CUCLP patient group (Spearman's rank correlation coefficient = .517, P = .034). Increase of nestinpositive structures suggests its role in the regulation of the remodeling of tissue in both CUCLP and CBCLP affected tissue. Dominance of Sox3 positivity in cleft affected epithelium indicates its possible role in (compensatory) formation of defective oral epithelium of CUCLP and CBCLP patients. The reduced expression of Dlx-4 implicates its limited regulatory role on the craniofacial development in CUCLP and CBCLP affected tissue.

La falla en la fusión de los procesos nasal y maxilar son causante de la fisura labiopalatina (FLP), que es uno de los defectos congénitos más comunes. La morfopatogenia de esta patología es multifactorial y aún poco clara. El objetivo de este estudio fue evaluar la presencia de nestina, el factor transcriptor SOX3 (Sox3) y la proteína homeobox DLX-4 (Dlx-4) en todo el tejido facial afectado por FLP bilateral unilateral (FU) y bilateral completa (FB). Se obtuvieron muestras de tejido de mucosa oral de 17 pacientes FUFLP y 13 FBFLP durante la corrección quirúrgica de la fisura y de 6 sujetos de control no afectados. Las secciones de tejido obtenidas se tiñeron con hematoxilina y eosina y mediante inmunohistoquímica para nestina, Sox3 y Dlx-4. La intensidad de la tinción fue graduada semicuantitativamente. Se detectaron estructuras positivas para nestina en todas las muestras de tejido de pacientes FUFLP y FBFLP, variando desde un número moderado a numerosas estructuras positivas para nestina. La inmunorreactividad de Sox3 fue más prominente en las células epiteliales en ambos grupos de pacientes con distribución frecuentemente irregular. Se observó un número principalmente moderado de células Dlx-4-positivas en la mayoría de las muestras de tejido. Se encontró una correlación positiva moderada estadísticamente significativa entre los factores de nestina y Sox3 en el grupo de pacientes FUFLP (coeficiente de correlación de rangos de Spearman = 0,517, P = 0,034). El aumento de estructuras positivas para nestina sugiere su papel en la regulación de la remodelación de tejido, tanto en tejido afectado por FUFLP como FBFLP. La dominancia de la positividad de Sox3 en el epitelio afectado de la fisura, indica su posible papel en la formación (compensatoria) del epitelio oral defectuoso de pacientes FUFLP y FBFLP. La expresión reducida de Dlx-4 implica su función reguladora limitada en el desarrollo craneofacial en tejido afectado por FUFLP y FBFLP.

Cleft Lip/metabolism , Cleft Palate/metabolism , Homeodomain Proteins/metabolism , SOXB1 Transcription Factors/metabolism , Nestin/metabolism , Immunohistochemistry
Article in Chinese | WPRIM | ID: wpr-689635


<p><b>OBJECTIVE</b>To study the association between the prevalence of overweight/obesity and copy number variations (CNVs) among Han, Uyghur, and Kazak children in Xinjiang, China.</p><p><b>METHODS</b>The kindergartens in Ili, Altay, and Karamay in Xinjiang were selected as research sites, and stratified cluster sampling was used to select the children aged 3-7 years. Body height and body weight were measured, and exfoliated buccal mucosa cells were collected. CNVplex® was used to measure the CNVs of FTO_1, IRX3_1, IRX3_2, MC4R_1, and MC4R_2.</p><p><b>RESULTS</b>A total of 603 children were surveyed (307 boys and 296 girls). There were 261 Han children, 194 Uyghur children, and 148 Kazak children. The overweight/obesity rates in Han, Uyghur, and Kazak children were 28.3%, 10.3%, and 31.1%, respectively (P<0.001). In Kazak children, the CNVs of IRX3_1 and MC4R_2 were associated with overweight/obesity (P<0.05). The multivariate logistic regression analysis showed that the risk of overweight/obesity in Han and Kazak children was 3.443 times (95%CI: 2.016-5.880) and 3.924 times (95%CI: 2.199-7.001), respectively, that in Uyghur children. The CNV of IRX3_1 was a risk factor for overweight/obesity (P=0.028, OR=2.251, 95%CI: 1.418-5.651).</p><p><b>CONCLUSIONS</b>The CNV of IRX3_1 is associated with overweight/obesity in Han, Uyghur, and Kazak children, and the association between the CNV of IRX3_1 and overweight/obesity in Kazak children should be taken seriously.</p>

Child , Child, Preschool , China , Ethnology , DNA Copy Number Variations , Female , Homeodomain Proteins , Genetics , Humans , Logistic Models , Male , Obesity , Genetics , Overweight , Genetics , Risk Factors , Transcription Factors , Genetics
Rev. Assoc. Med. Bras. (1992) ; 63(7): 656-661, July 2017. tab, graf
Article in English | LILACS | ID: biblio-896374


Summary Introduction: Prostate cancer is the second type of cancer diagnosed and the fifth cause of death in men worldwide. Early diagnosis helps to control disease progression. Currently, prostate specific antigen is the standard biomarker, as it has a broad scope of identification and, thus, new and more specific biomarkers must be studied. Objective: To evaluate the accuracy of engrailed-2 protein (EN2) in urine as a prostate cancer biomarker. Method: A comprehensive search was conducted in the period from January 2005 to July 2016 using the following electronic databases: Medline (PubMed), Embase, Cochrane Library and Lilacs. The keywords used in the databases were: "engrailed-2," "EN2," "prostatic neoplasms." The search was limited to humans and there was no language restriction. Critical appraisal of the included studies was performed according to Quadas-2. Statistical analysis was performed using Meta-DiSc® and RevMan 5.3 softwares. Results: A total of 248 studies were identified. After title and abstract screening, 231 studies were removed. A total of 17 studies were read in full and two studies were included in the meta-analysis. The pooled sensitivity was 66% (95CI 0.56-0.75) and specificity was 89% (95CI 0.86-0.92). The DOR was 15.08 (95CI 8.43-26.97). Conclusion: The EN2 test showed high specificity (89%) and low sensitivity (66%).

Resumo Introdução: O câncer de próstata é o segundo tipo de câncer diagnosticado e a quinta causa de morte em homens em todo o mundo. O diagnóstico precoce é fundamental para o prognóstico da doença. Atualmente, o antígeno específico da próstata (PSA) é o biomarcador mais utilizado; porém, biomarcadores mais específicos devem ser estudados. Objetivo: Avaliar a acurácia da proteína engrenada-2 (EN2) na urina como biomarcador de câncer de próstata. Método: Foi realizada uma busca abrangente no período de janeiro de 2005 a julho de 2016, utilizando as seguintes bases de dados eletrônicas: Medline (PubMed), Embase, Cochrane Library e Lilacs. As palavras-chave utilizadas foram: "engrailed-2", "EN2", "prostatic neoplasms". A busca foi limitada a humanos e não houve restrição de idioma. A avaliação da qualidade dos estudos incluídos foi realizada de acordo com Quadas-2. A análise estatística foi realizada usando o software Meta-DiSc® e RevMan 5.3. Resultados: Foram identificados 248 estudos. Após a triagem dos títulos e resumos, foram excluídos 231. Um total de 17 foram lidos na íntegra e dois, incluídos na metanálise. A sensibilidade combinada foi de 66% (IC95% 0,56-0,75). A especificidade foi de 89% (IC95% 0,86-0,92). O DOR foi de 15,08 (IC95% 8,43-26,97). Conclusão: O teste EN2 mostrou alta especificidade (89%) e baixa sensibilidade (66%).

Prostatic Neoplasms , Homeodomain Proteins/urine , Nerve Tissue Proteins/urine , Biomarkers, Tumor/urine , Predictive Value of Tests , Sensitivity and Specificity , Prostate-Specific Antigen/blood , Disease Progression
Biol. Res ; 50: 31, 2017. graf
Article in English | LILACS | ID: biblio-950882


BACKGROUND: MiR-320 is downregulated in multiple cancers, including glioma and acts as tumor suppressor through inhibiting tumor cells proliferation and inducing apoptosis. PBX3 (Pre-B cell leukemia homeobox 3), a putative target gene of miR-320, has been reported to be upregulated in various tumors and promote tumor cell growth through regulating MAKP/ERK pathway. This study aimed to verify whether miR-320 influences glioma cells growth through regulating PBX3. METHODS: Twenty-four human glioma and paired adjacent nontumorous tissues were collected for determination of miR-320 and PBX3 expression using RT-qPCR and western blot assays. Luciferase reporter assay was performed to verify the interaction between miR-320 and its targeting sequence in the 3' UTR of PBX3 in glioma cells U87 and U251. Increased miR-320 level in U87 and U251 cells was achieved through miR-320 mimic transfection and the effect of which on glioma cells growth, proliferation, cell cycle, apoptosis and activation of Raf-1/MAPK pathway was determined using MTT, colony formation, flow cytometry and western blot assays. PBX3 knockdown was performed using shPBX3 and the influence on MAPK pathway activation was evaluated. RESULTS: MiR-320 downregulation and PBX3 upregulation was found in glioma tissues. Luciferase reporter assays identified miR-320 directly blinds to the 3' UTR of PBX3 in glioma cells. MiR-320 mimic transfection suppressed glioma cells proliferation, and induced cell cycle arrest and apoptosis. Both miR-320 overexpression and PBX3 knockdown inhibited Raf-1/MAPK activation. CONCLUSION: MiR-320 may suppress glioma cells growth and induced apoptosis through the PBX3/Raf-1/MAPK axis, and miR-320 oligonucleotides may be a potential cancer therapeutic for glioma.

Humans , Brain Neoplasms/metabolism , Proto-Oncogene Proteins/metabolism , Homeodomain Proteins/metabolism , MicroRNAs/metabolism , Glioma/metabolism , Brain Neoplasms/pathology , Down-Regulation , Gene Expression Regulation, Neoplastic , Cell Differentiation/drug effects , Up-Regulation , Cell Line, Tumor , Cell Proliferation/drug effects , Glioma/pathology
Cell Journal [Yakhteh]. 2016; 18 (1): 21-27
in English | IMEMR | ID: emr-178842


Objective: Cutaneous melanoma is the most hazardous malignancy of skin cancer with a high mortality rate. It has been reported that cancer stem cells [CSCs] are responsible for malignancy in most of cancers including melanoma. The aim of this study is to compare two common methods for melanoma stem cell enriching; isolating based on the CD133 cell surface marker and spheroid cell culture

Materials and Methods: In this experimental study, melanoma stem cells were enriched by fluorescence activated cell sorting [FACS] based on the CD133 protein expression and spheroid culture of D10 melanoma cell line,. To determine stemness features, the mRNA expression analysis of ABCG2, c-MYC, NESTIN, OCT4-A and -B genes as well as colony and spheroid formation assays were utilized in unsorted CD133+, CD133- and spheroid cells. Significant differences of the two experimental groups were compared using student's t tests and a two-tailed value of P<0.05 was statistically considered as a significant threshold

Results: Our results demonstrated that spheroid cells had more colony and spheroid forming ability, rather than CD133+ cells and the other groups. Moreover, melanospheres expressed higher mRNA expression level of ABCG2, c-MYC, NESTIN and OCT4-A compared to other groups [P<0.05]

Conclusion: Although CD133+ derived melanoma cells represented stemness features, our findings demonstrated that spheroid culture could be more effective method to enrich melanoma stem cells

Peptides , Antigens, CD , Melanoma , Homeodomain Proteins , Transcription Factors , Stem Cells , Cell Line , Spheroids, Cellular , Cells, Cultured