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1.
Asian Journal of Andrology ; (6): 186-190, 2022.
Article in English | WPRIM | ID: wpr-928536

ABSTRACT

Nonobstructive azoospermia (NOA) is a common cause of infertility and is defined as the complete absence of sperm in ejaculation due to defective spermatogenesis. The aim of this study was to identify the genetic etiology of NOA in an infertile male from a Chinese consanguineous family. A homozygous missense variant of the membrane-bound O-acyltransferase domain-containing 1 (MBOAT1) gene (c.770C>T, p.Thr257Met) was found by whole-exome sequencing (WES). Bioinformatic analysis also showed that this variant was a pathogenic variant and that the amino acid residue in MBOAT1 was highly conserved in mammals. Quantitative polymerase chain reaction (Q-PCR) analysis showed that the mRNA level of MBOAT1 in the patient was 22.0% lower than that in his father. Furthermore, we screened variants of MBOAT1 in a broader population and found an additional homozygous variant of the MBOAT1 gene in 123 infertile men. Our data identified homozygous variants of the MBOAT1 gene associated with male infertility. This study will provide new insights for researchers to understand the molecular mechanisms of male infertility and will help clinicians make accurate diagnoses.


Subject(s)
Acetyltransferases/genetics , Animals , Azoospermia/genetics , Cell Cycle Proteins/genetics , Humans , Infertility, Male/genetics , Male , Mammals , Membrane Proteins/genetics , Mutation
2.
Article in Chinese | WPRIM | ID: wpr-928432

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a child with myopathy and cerebellar atrophy with ataxia.@*METHODS@#Clinical examinations and laboratory testing were carried out for the patient. The proband and the parents' genomic DNA was extracted from peripheral blood samples and subjected to trio whole-exome sequencing. Candidate variant was validated by Sanger sequencing.@*RESULTS@#The 1-year-and-8-month-old boy manifested motor developmental delay, ataxia, hypomyotonia, increased serum creatine kinase. Cranial MRI showed cerebellar atrophy with progressive aggravation. Genetic testing revealed that the patient has harbored compound heterozygous variants of the MSTO1 gene, namely c.13delG (p.Ala5ProfsTer68) and c.971C>T (p.Thr324Ile), which were respectively inherited from his mother and father. The former was unreported previously and was predicted to be likely pathogenic, whilst the latter has been reported previously and was predicted to be of uncertain significance.@*CONCLUSION@#The compound heterozygous c.13delG (p.Ala5ProfsTer68) and c.971C>T (p.Thr324Ile) variants probably underlay the disease in the proband. Above finding has enriched the spectrum of MSTO1 gene variants underlying mitochondrial myopathy and cerebellar atrophy with ataxia.


Subject(s)
Ataxia/genetics , Atrophy/genetics , Cell Cycle Proteins/genetics , Child , Cytoskeletal Proteins/genetics , Humans , Infant , Male , Mitochondrial Myopathies , Mutation , Neurodegenerative Diseases , Whole Exome Sequencing
3.
Article in Chinese | WPRIM | ID: wpr-928308

ABSTRACT

OBJECTIVE@#Osteosarcoma(OS) and Ewing's sarcoma (EWS) are the two most common primary malignant bone tumors in children. The aim of the study was to identify key genes in OS and EWS and investigate their potential pathways.@*METHODS@#Expression profiling (GSE16088 and GSE45544) were obtained from GEO DataSets. Differentially expressed genes were identified using GEO2R and key genes involved in the occurrence of both OS and EWS were selected using venn diagram. Gene ontology and pathway enrichment analyses were performed for the ensembl. Protein-protein interaction (PPI) networks were established by STRING. Further, UCSC was used to predict the transcription factors of the cell division cycke 5-like(CDC5L) gene, and GEPIA was used to analyze the correlation between the transcription factors and the CDC5L gene.@*RESULTS@#The results showed that CDC5L gene was the key gene involved in the pathogenesis of OS and EWS. The gene is mainly involved in mitosis, and is related to RNA metabolism, processing of capped intron-containing pre-mRNA, mRNA and pre-mRNA splicing.@*CONCLUSION@#CDC5L, as a key gene, plays a role in development of OS and EWS, which may be reliable targets for diagnosis and treatment of these primary malignant tumors.


Subject(s)
Bone Neoplasms/pathology , Cell Cycle Proteins/genetics , Child , Computational Biology , Gene Expression Profiling , Humans , Osteosarcoma/genetics , RNA-Binding Proteins/genetics , Sarcoma, Ewing/genetics
4.
Article in Chinese | WPRIM | ID: wpr-927858

ABSTRACT

Aurora kinase A (AURKA),a family member of aurora kinases,is involved in mitotic entry,maturation and separation of centrosome,assembly and stabilization of bipolar spindle,and condensation and separation of chromosome.Studies have demonstrated that AURKA plays a similar role in meiosis,while the specific mechanism and the similarities and differences in its role between meiosis and mitosis remain unclear.Therefore,we reviewed the studies about the localization and activation of AURKA in oocyte meiosis,and compared the role of AURKA in regulating spindle formation,activating spindle assembly checkpoint,and correcting the kinetochore-microtubule attachment between the meiosis of oocytes and the mitosis of somatic cells.This review will lay a theoretical foundation for revealing the mechanism of AURKA in the regulation of cell division and for the clinical research related to cancer and reproduction.


Subject(s)
Aurora Kinase A/genetics , Cell Cycle Proteins/genetics , Chromosome Segregation , Humans , Meiosis , Oocytes
5.
Article in Chinese | WPRIM | ID: wpr-922013

ABSTRACT

OBJECTIVE@#To explore the genetic etiology of a neonate with suggestive features of Cornelia de Lange Syndrome (CdLS).@*METHODS@#Chromosome karyotyping, copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the child. Meanwhile, peripheral venous blood samples were taken from his parents for verifying the suspected pathogenic variants detected in the child.@*RESULTS@#The child has exhibited developmental delay, microcephaly, ptosis, micrognathia, and low ear setting, and was suspected as CdLS. No abnormality was found by karyotyping and CNV-seq analysis. WES has detected 5 heterogeneous variants and 1 hemizygous variant on the X chromosome. Combining the genetic pattern and result of family verification, a hemizygous C.3500T>C (p.ile1167thr) of the SMC1A gene was predicted to underlay the clinical manifestations of the patient. This variant was not recorded in the dbSNP and gnomAD database. PolyPhen2, Provean, SIFT all predicted the variant to be harmful, and PhastCons conservative prediction is was a conservative mutation. ACMG variant classification standard evidence supports are PM2, PP2, and PP3.@*CONCLUSION@#The novel c.3500T>C (p.Ile1167Thr) missense mutation of the SMC1A gene probably underlay the genetic etiology of CdLS in this child. Above results has enriched the mutation spectrum of CdLS type II, and facilitated clinical counseling for this family.


Subject(s)
Cell Cycle Proteins/genetics , Child , DNA Copy Number Variations , De Lange Syndrome/genetics , Humans , Infant, Newborn , Mutation , Phenotype , Whole Exome Sequencing
6.
Journal of Experimental Hematology ; (6): 1129-1135, 2021.
Article in Chinese | WPRIM | ID: wpr-888528

ABSTRACT

OBJECTIVE@#To investigate the effect of CDK1 interference regulation of PLK1, Aurora B and TRF1 on the proliferation of leukemia cells.@*METHODS@#The human myelogenous leukemia cell line HL-60 was selected as the research object, and the effect of TRF1 expression and its changes on cell proliferation and cycle was investigated by regulating intracellular CDK1 expression. The objects were divided into 5 groups, including control group, shRNA-NC group, CDK1-shRNA group, pcDNA group and pcDNA-CDK1 group. RT-PCR was used to detect the CDK1 expression of cells in each group; colony formation was used to detect the proliferation of the cells. Western blot was used to detect the expression of CDK1, PLK1, Aurora B, TRF1, and cyclin p53, p27, cyclinA.@*RESULTS@#The phosphorylation level of PLK1, Aurora B and the expression of TRF1 in the CDK1-shRNA group were significantly down-regulated as compared with those in the control group (P<0.05). Compared with the control group, the cells in CDK1-shRNA group showed lower clone formation rate, the increasing of cycle-associated proteins p53 and p27 and the decreasing of cyclinA expression (P<0.05). It was shown that interfered CDK1 expression could inhibit the proliferation of HL-60 cells and prolong the time that they enter mitosis, thereby extending the cell cycle. Compared with the control group, the overexpressed CDK1 in the pcDNA-CDK1 group made the phosphorylation level of PLK1, Aurora B, and TRF1 expression increase significantly (P<0.05), also the colony formation rate (P<0.05). The cycle-related proteins p53 and p27 was down-regulated, while cyclinA expression was up-regulate significantly (P<0.05). The results indicted that overexpressed CDK1 could stimulate adverse reactions, thereby promoting the proliferation of HL-60 cells and shortening the cell cycle.@*CONCLUSION@#Knocking out CDK1 can inhibit the phosphorylation of PLK1 and Aurora B and negatively regulate TRF1, thereby inhibiting the proliferation of leukemia cells.


Subject(s)
CDC2 Protein Kinase , Cell Cycle Proteins/genetics , Cell Proliferation , Humans , Leukemia , Mitosis , Phosphorylation , Proto-Oncogene Proteins/genetics
7.
Article in Chinese | WPRIM | ID: wpr-879534

ABSTRACT

OBJECTIVE@#To explore the genetic basis for 7 patients with Alström syndrome.@*METHODS@#DNA was extracted from peripheral blood samples of the patients and their parents. Whole exome sequencing was carried out for the patients. Suspected variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#Genetic testing revealed 12 variants of the ALMS1 gene among the 7 patients, including 7 nonsense and 5 frameshift variants, which included c.5418delC (p.Tyr1807Thrfs*23), c.10549C>T (p.Gln3517*), c.9145dupC (p.Thr3049Asnfs*12), c.10819C>T (p.Arg3607*), c.5701_5704delGAGA (p.Glu1901Argfs*18), c.9154_9155delCT (p.Cys3053Serfs*9), c.9460delG (p.Val3154*), c.9379C>T (p.Gln3127*), c.12115C>T (p.Gln4039*), c.1468dupA (p.Thr490Asnfs*15), c.10825C>T (p.Arg3609*) and c.3902C>A (p.Ser1301*). Among these, c.9154_ 9155delCT, c.9460delG, c.9379C>T, and c.1468dupA were unreported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.9379C>T and c.12115C>T variants of the ALMS1 gene were predicted to be likely pathogenic (PVS1+PM2), whilst the other 10 variants were predicted to be pathogenic (PVS1+ PM2+ PP3+PP4).@*CONCLUSION@#ALMS1 variants probably underlay the Alström syndrome in the 7 patients, and genetic testing can provide a basis for the clinical diagnosis of this syndrome. The discovery of four novel variants has expanded the mutational spectrum of Alström syndrome.


Subject(s)
Alstrom Syndrome/genetics , Cell Cycle Proteins/genetics , Humans , Mutation , Pedigree , Whole Exome Sequencing
8.
Article in Chinese | WPRIM | ID: wpr-879525

ABSTRACT

OBJECTIVE@#To carry out genetic testing for an abortus suspected with Cornelia de Lange syndrome (CdLS).@*METHODS@#History of gestation and the family was taken. Combined with prenatal ultrasonography and the phenotype of the abortus, a diagnosis was made for the proband. Fetal tissue and peripheral blood samples of its parents were collected for the extraction of genomic DNA. Whole exome sequencing was carried out to detect mutations related to the phenotype. Suspected mutations were verified in the parents through Sanger sequencing.@*RESULTS@#Prenatal ultrasound found that the forearms and hands of the fetus were anomalous, in addition with poorly formed vermis cerebellum, slight micrognathia, and increased echo of bilateral renal parenchyma. Examination of the abortus has noted upper limb and facial malformations. Whole exome sequencing revealed that the fetus carried a heterozygous c.2118delG (p.Lys706fs) frameshift mutation of the NIPBL gene. The same mutation was not found in either parent.@*CONCLUSION@#The heterozygous c.2118delG (p.Lys706fs) frameshift mutation of the NIPBL gene probably underlies the CdLS in the fetus. Above finding has provided a basis for the genetic counseling for the family.


Subject(s)
Cell Cycle Proteins/genetics , DNA Mutational Analysis , De Lange Syndrome/pathology , Female , Fetus , Humans , Male , Mutation , Phenotype , Pregnancy , Whole Exome Sequencing
9.
Rev. invest. clín ; 72(6): 372-379, Nov.-Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1289732

ABSTRACT

Abstract Background: Ovarian cancer is the most lethal gynecologic cancer. Although most patients respond adequately to the first-line therapy, up to 85% experience a recurrence of disease, which carries a poor prognosis. Mitotic arrest deficiency 1 is a protein that helps in the assembly of the mitotic spindle assembly checkpoint by preventing anaphase until all chromatids are properly aligned. A single-nucleotide polymorphism in the MAD1L1 gene is prevalent in patients with advanced epithelial ovarian cancer and alters the way in which it responds to chemotherapy. Objective: The objective of the study was to study the relationship between the rs1801368 polymorphism of MAD1L1 and prognosis of ovarian adenocarcinoma. Methods: A total of 118 patients in whom the MAD1L1 gene was sequenced were analyzed using descriptive and comparative statistics. Results: Patients carrying the wild-type genotype had a higher distribution of early-stage disease. Having a MAD1L1 polymorphic allele increased the risk of being non-sensitive to chemotherapy. The median disease-free survival for patients with the wild-type MAD1L1 was 46.93 months, compared to 10.4 months for patients with at least one polymorphic allele. Conclusions: The rs1801368 polymorphism of MAD1L1 gene worsens prognosis in patients with ovarian adenocarcinoma. Traditional therapy for ovarian cancer might not be optimal in patients carrying this polymorphism.


Subject(s)
Humans , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Ovarian Neoplasms/genetics , Adenocarcinoma/genetics , Cell Cycle Proteins/genetics , Polymorphism, Single Nucleotide , Ovarian Neoplasms/mortality , Prognosis , Adenocarcinoma/mortality , Survival Rate , Retrospective Studies
10.
Biol. Res ; 53: 41, 2020. graf
Article in English | LILACS | ID: biblio-1131885

ABSTRACT

BACKGROUND: Tumor angiogenesis is an essential event for tumor growth and metastasis. It has been showed that REC8, a component of the meiotic cohesion complex, played a vital role in Epithelial-Mesenchymal Transition (EMT) in gastric cancer. However, the role of REC8 in gastric cancer angiogenesis remains to be identified. RESULTS: Inhibition of REC8 expression in gastric cancer cells contributed to tumor angiogenesis in the gastric cancer microenvironment. The clinical analysis demonstrated that the loss of REC8 in gastric cancer with enrichment of MVD. Depletion of REC8 expression in gastric cancer cells significantly increased tube formation of human umbilical vein endothelial cells (HUVECs), which is attributed to enhancement of vascular endothelial growth factor (VEGF) secretion caused by REC8 slicing. While addition of neutralizing antibody targeted VEGF into supernatant drastically reversed the effect of REC8 loss in gastric cancer cells on tube formation. Mechanistic analyses indicated that ablation of REC8 promotes nuclear factor-κB (NF-κB) p65 activity and its downstream gene VEGF expression, leading to tube formation. CONCLUSIONS: These results demonstrated a novel REC8 function that suppressed tumor angiogenesis and progression by attenuation of VEGF in gastric cancer microenvironment.


Subject(s)
Humans , Stomach Neoplasms/pathology , NF-kappa B/genetics , Cell Cycle Proteins/genetics , Vascular Endothelial Growth Factor A/genetics , Neovascularization, Pathologic/genetics , Stomach Neoplasms/blood supply , Cell Line, Tumor , Tumor Microenvironment , Human Umbilical Vein Endothelial Cells
11.
Article in Chinese | WPRIM | ID: wpr-880765

ABSTRACT

OBJECTIVE@#To screen the key genes related to the prognosis of lung adenocarcinoma through big data analysis and explore their clinical value and potential mechanism.@*METHODS@#We analyzed GSE18842, GSE27262, and GSE33532 gene expression profile data obtained from the Gene Expression Omnibus (GEO). Bioinformatics methods were used to screen the differentially expressed genes in lung adenocarcinoma tissues and KEGG and GO enrichment analysis was performed, followed by PPI interaction network analysis, module analysis, differential expression analysis, and prognosis analysis. The expressions of MAD2L1 and TTK by immunohistochemistry were verified in 35 non-small cell lung cancer specimens and paired adjacent tissues.@*RESULTS@#We identified a total of 256 genes that showed significant differential expressions in lung adenocarcinoma, including 66 up-regulated and 190 down-regulated genes. Thirty-two up-regulated core genes were screened by functional analysis, and among them 29 were shown to significantly correlate with a poor prognosis of patients with lung adenocarcinoma. All the 29 genes were highly expressed in lung adenocarcinoma tissues compared with normal lung tissues and were mainly enriched in cell cycle pathways. Seven of these key genes were closely related to the spindle assembly checkpoint (SAC) complex and responsible for regulating cell behavior in G2/M phase. We selected SAC-related proteins TTK and MAD2L1 to test their expressions in clinical tumor samples, and detected their overexpression in lung adenocarcinoma tissues as compared with the adjacent tissues.@*CONCLUSIONS@#Seven SAC complex-related genes, including TTK and MAD2L1, are overexpressed in lung adenocarcinoma tissues with close correlation with the prognosis of the patients.


Subject(s)
Adenocarcinoma of Lung/genetics , Big Data , Cell Cycle Proteins/genetics , Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , M Phase Cell Cycle Checkpoints , Mad2 Proteins/genetics , Protein Serine-Threonine Kinases/genetics , Protein-Tyrosine Kinases/genetics
12.
Chinese Journal of Biotechnology ; (12): 2298-2312, 2020.
Article in Chinese | WPRIM | ID: wpr-878487

ABSTRACT

Polo-like kinase 1 (Plk1) is widely regarded as one of the most promising targets for cancer therapy due to its essential role in cell division and tumor cell survival. At present, most Plk1 inhibitors have been developed based on kinase domain, some of which are in clinical trial. However, inhibitors targeting kinase domain face off-target effect and drug resistance owing to the conserved nature and the frequent mutations in the ATP-binding pocket. In addition to a highly conserved kinase domain, Plk1 also contains a unique Polo-Box domain (PBD), which is essential for Plk1's subcellular localization and mitotic functions. Inhibitors targeting Plk1 PBD show stronger selectivity and less drug resistance for cancer therapy. Therefore, Plk1 PBD is an attractive target for the development of anti-cancer agents. In this review, we will summarize the up-to date drug discovery for targeting Plk1 PBD, including the molecular structure and cellular functions of Plk1 PBD. Small-molecule inhibitors targeting Plk1 PBD not only provide an opportunity to specifically inhibit Plk1 activity for cancer treatment, but also unveil novel biological basis regarding the molecular recognition of Plk1 and its substrates.


Subject(s)
Cell Cycle Proteins/genetics , Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacology , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins/genetics
13.
Rev. bras. ginecol. obstet ; 40(10): 606-613, Oct. 2018. graf
Article in English | LILACS | ID: biblio-977778

ABSTRACT

Abstract Objective The aim of the present study was to analyze the expression of the CD63, S100A6, and GNB2L1genes, which participate in mechanisms related to the complex pathophysiology of endometriosis. Methods A case-control study was conducted with 40 women who were diagnosed with endometriosis, and 15 fertile and healthy women. Paired samples of eutopic endometrium and endometriotic lesions (peritoneal and ovarian endometriotic implants) were obtained from the women with endometriosis in the proliferative (n = 20) or secretory phases (n = 20) of the menstrual cycle. As controls, paired endometrial biopsy samples were collected from the healthy women in the proliferative (n = 15) and secretory (n = 15) phases of the samemenstrual cycle.We analyzed the expression levels of the CD63, S100A6, and GNB2L1 genes by real-time polymerase chain reaction. Results An increase in CD63, S100A6, and GNB2L1 gene transcript levels was observed in the ectopic implants compared with the eutopic endometrium of the women with and without endometriosis, regardless of the phase of the menstrual cycle. Conclusion These findings suggest that the CD63, S100A6, and GNB2L1 genesmay be involved in the pathogenesis of endometriosis, since they participate in mechanisms such as inhibition of apoptosis, angiogenesis and cell proliferation, which lead to the loss of cell homeostasis in the ectopic endometrium, thus contributing to the implantation and survival of the tissue in the extrauterine environment.


Resumo Objetivo O objetivo do presente estudo foi analisar a expressão dos genes CD63, S100A6 e GNB2L1, que participam em mecanismos relacionados à complexa fisiopatologia da endometriose. Métodos Um estudo caso-controle foi realizado com 40 mulheres diagnosticadas com endometriose e 15 mulheres férteis e saudáveis. Amostras pareadas de endométrio eutópico e de lesões endometrióticas (implantes endometrióticos peritoneais e ovarianos) foram obtidas de mulheres com endometriose nas fases proliferativa (n = 20) ou secretora (n = 20) do ciclo menstrual. Como controle, amostras pareadas de biópsia endometrial foram coletadas de mulheres saudáveis nas fases proliferativa (n = 15) e secretora (n = 15) nomesmo ciclomenstrual. Foram analisados os níveis de expressão dos genes CD63, S100A6 e GNB2L1 por reação em cadeia da polimerase em tempo real. Resultados Foi observado um aumento nos níveis de transcritos dos genes CD63, S100A6 e GNB2L1 em implantes ectópicos quando comparado ao endométrio eutópico de mulheres com e sem endometriose, independente da fase do ciclo menstrual. Conclusão Estes achados sugerem que os genes CD63, S100A6 e GNB2L1 podem estar envolvidos na patogênese da endometriose, pois participam de mecanismos como inibição de apoptose, angiogênese e proliferação celular, os quais levam à perda da homeostase celular no endométrio ectópico e, portanto, contribuem para o implante e a sobrevivência do tecido no ambiente extrauterino.


Subject(s)
Humans , Female , Adult , Apoptosis/genetics , Cell Cycle Proteins/genetics , Cell Proliferation/genetics , Endometriosis/genetics , Endometriosis/pathology , Tetraspanin 30/genetics , S100 Calcium Binding Protein A6/genetics , Receptors for Activated C Kinase/genetics , Neoplasm Proteins/genetics , Neovascularization, Pathologic/genetics , Case-Control Studies , Gene Expression
14.
Biol. Res ; 51: 44, 2018. tab, graf
Article in English | LILACS | ID: biblio-983945

ABSTRACT

BACKGROUND: Emerging evidence indicate that miRNAs play an important role on gastric cancer (GC) progression via regulating several downstream targets, but it is still partially uncovered. This study aimed to explore the molecular mechanisms of GC by comprehensive analysis of mRNAs and miRNA expression profiles. METHODS: The mRNA and miRNA expression profiles of GSE79973 and GSE67354 downloaded from Gene Expression Omnibus were used to analyze the differentially expressed genes (DEGs) and DE-miRNAs among GC tissues and normal tissues. Then, targets genes of DE-miRNAs were predicted and the DE-miRNA-DEG regulatory network was constructed. Next, function enrichment analysis of the overlapped genes between the predicted DE-miRNAs targets and DEGs was performed and a protein-protein interactions network of overlapped genes was constructed. Finally, RT-PCR analysis was performed to detect the expression levels of several key DEGs and DE-miRNAs. RESULTS: A set of 703 upregulated and 600 downregulated DEGs, as well as 8 upregulated DE-miRNAs and 27 downregulated DE-miRNAs were identified in GC tissue. hsa-miR-193b-3p and hsa-miR-148a-3p, which targeted most DEGs, were highlighted in the DE-miRNA-DEG regulatory network, as well as hsa-miR-1179, which targeted KNL1, was newly predicted to be associated with GC. In addition, NCAPG, which is targeted by miR-193b-3p, and KNL1, which is targeted by hsa-miR-1179, had higher degrees in the PPI network. RT-qPCR results showed that hsa-miR-148a-3p, hsa-miR-193b-3p, and hsa-miR-1179 were downregulated, and NCAPG and KNL1 were upregulated in GC tissues; this is consistent with our bioinformatics-predicted results. CONCLUSIONS: The downregulation of miR-193b-3p might contribute to GC cell proliferation by mediating the upregulation of NCAPG; as additionally, the downregulation of miR-193b-3p might contribute to the mitotic nuclear division of GC cells by mediating the upregulation of KNL1.


Subject(s)
Humans , Stomach Neoplasms/metabolism , Gene Expression Regulation, Neoplastic/genetics , Up-Regulation/genetics , Cell Cycle Proteins/metabolism , MicroRNAs/metabolism , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Biomarkers, Tumor/genetics , Disease Progression , Cell Cycle Proteins/genetics , Gene Expression Profiling , Real-Time Polymerase Chain Reaction , Microtubule-Associated Proteins/metabolism
15.
Biol. Res ; 49: 1-10, 2016. ilus, graf, tab
Article in English | LILACS | ID: lil-774432

ABSTRACT

BACKGROUND: Reprimo (RPRM), a highly glycosylated protein, is a new downstream effector of p53-induced cell cycle arrest at the G2/M checkpoint, and a putative tumor suppressor gene frequently silenced via methylation of its promoter region in several malignances. The aim of this study was to characterize the epigenetic inactivation and its biological function in BC cell lines. METHODS: The correlation between RPRM methylation and loss of mRNA expression was assessed in six breast cancer cell lines by methylation specific PCR (MSP), 5'-Aza-2'-deoxycytidine treatment and RT-PCR assays. MDA-MB-231 cells were chosen to investigate the phenotypic effect of RPRM in cell proliferation, cell cycle, cell death, cell migration and invasion. RESULTS: In the cancer methylome system (CMS) (web-based system for visualizing and analyzing genome-wide methylation data of human cancers), the CpG island region of RPRM (1.1 kb) was hypermethylated in breast cancer compared to normal breast tissue; more interesting still was that ERa(+) tumors showed higher methylation intensity than ERa(-). Downregulation of RPRM mRNA by methylation was confirmed in MDA-MB-231 and BT-20 cell lines. In addition, overexpression of RPRM in MDA-MB-231 cells resulted in decreased rates of cell migration, wound healing and invasion in vitro. However, RPRM overexpression did not alter cell viability, phosphatidylserine (PS) translocation or G2/M cell cycle transition. CONCLUSION: Taken together, these data suggest that RPRM is involved in decreased cell migration and invasion in vitro, acting as a potential tumor suppressor gene in the MDA-MB-231 cell line.


Subject(s)
Female , Humans , Breast Neoplasms/pathology , Cell Cycle Proteins/physiology , Cell Movement/physiology , Cell Proliferation/physiology , Glycoproteins/physiology , Analysis of Variance , Blotting, Western , Breast Neoplasms/genetics , Cell Cycle , Cell Line, Tumor , Cell Survival , Cell Cycle Proteins/genetics , Cell Movement/genetics , Cell Proliferation/genetics , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Glycoproteins/genetics , Neoplasm Invasiveness , Real-Time Polymerase Chain Reaction , Statistics, Nonparametric
16.
Egyptian Journal of Hospital Medicine [The]. 2016; 62 (January): 9-17
in English | IMEMR | ID: emr-180255

ABSTRACT

Background: examining the alteration of cell cycle genes in early hepatitis C virus [HCV] found that altered expression of mitotic checkpoint genes, MAD2L1, KNTC1, CDC16 and CDC34, KNTC1 known as "rough deal protein" [ROD] is part of a complex involved in elaborating an inhibitory signal due to improper chromosomal aligment during cell division


Aim of the work: attempt for the identification of proteins [genes], which act as predictive factors to identify patients with high risk of cell transformation and HCC development


Patients and Methods: fifty three patients with chronic HCV infection, age ranged between 18 and 58 years, time of assessment was before starting therapy of hepatitis C at the National Hepatology and Tropical Medicine Research Institute. Ten healthy individuals were included to serve as controls. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography, and collection of blood samples for routine laboratory investigation; CBCs. Liver biopsy was done to all patients and controls, patients revealed mild fibrosis [Metavir fibrosis scores from F1 to F3]. Also, we used freshly frozen liver biopsies mRNA levels with perspective protein levels of four genes: P27, P15, KNTC1, MAD2L1


Results: significant association of P27, P15, KNTC1 and MAD2L-1 with the progression of liver fibrosis in chronic HCV liver biopsy was found


Conclusion: there is altered gene expression in HCV-associated liver disease


Recommendations: The emerging interest of hepatologists in the influence of genetic factors in HCV. Evaluation of the expression of key proteins related to the cell cycle and apoptosis in chronically infected patients with HCV would be of significance to understand disease pathogenesis, and will help in identifying novel prognostic indicators


Subject(s)
Adult , Adolescent , Aged , Female , Humans , Male , Middle Aged , Cell Cycle Proteins/genetics , Cyclin-Dependent Kinase Inhibitor p15 , Microtubule-Associated Proteins , Mad2 Proteins , Cyclin-Dependent Kinase Inhibitor p27 , Cell Proliferation , Liver Cirrhosis/genetics
19.
Cad. saúde pública ; 31(3): 620-632, 03/2015. tab
Article in Portuguese | LILACS | ID: lil-744835

ABSTRACT

O estudo descreve os pontos de venda de alimentos e sua associação com sobrepeso/obesidade em escolares de Florianópolis, Santa Catarina, Brasil. Desenho transversal com amostra probabilística de 2.506 escolares de escolas públicas (n = 19) e privadas (n = 11). O sobrepeso/obesidade foi classificado pela referência da Organização Mundial da Saúde de 2007. Foram realizadas análises brutas e ajustadas por meio de regressão de Poisson. A prevalência de sobrepeso/obesidade foi de 34,2%. Na rede pública, foram verificados 19,6% de sobrepeso e 13,5% de obesidade. Na rede privada, observaram-se 22,4% de sobrepeso e 11,1% de obesidade. Na rede pública, foi encontrada associação entre sobrepeso/obesidade e utilização da padaria (p = 0,004). Na rede privada, observou-se que os escolares de famílias que utilizaram o supermercado apresentaram 26% menos de sobrepeso/obesidade do que os escolares que não utilizam esses pontos de venda de alimentos (p = 0,003). Os dados encontrados evidenciam a existência de associação entre a utilização de alguns tipos de pontos de venda de alimentos (supermercado e padaria) e a prevalência de sobrepeso/obesidade na população escolar.


The study analyzes retail food outlets and their association with overweight/obesity in schoolchildren from Florianópolis, Santa Catarina State, Brazil. The study used a cross-sectional design with a random sample of 2,506 schoolchildren from public (n = 19) and private schools (n = 11). Overweight and obesity were classified according to World Health Organization guidelines for 2007, and crude and adjusted analyses were performed using Poisson regression. Prevalence of overweight/obesity was 34.2%. In public schools, 19.6% of the children were overweight and 13.5% were obese, as compared to 22.4% and 11.1% in private schools. An association was found in the public school system between overweight/obesity and the use of bakeries for food purchases (p = 0.004). In the private school system, children of families that bought groceries at the supermarket showed 26% less overweight/obesity compared to those who did not (p = 0.003). The data show an association between some types of food outlets (supermarkets and bakeries) and prevalence of overweight/obesity in the school-age population.


El estudio describe los puntos de venta de alimentos y su asociación con el sobrepeso/obesidad en escolares de Florianópolis, Santa Catarina, Brasil. Se trata de un estudio transversal con una muestra aleatoria de 2.506 escolares de las escuelas públicas (n = 19) y privadas (n = 11). El sobrepeso/obesidad se clasifica, en función de la OMS en 2007, con análisis ajustados y crudos que se realizaron mediante la regresión de Poisson. La prevalencia de sobrepeso/obesidad fue de un 34,2%. En el sistema público el resultado fue de un 19,6% sobrepeso y un 13,5% obesidad. En el privado se observó un 22,4% de sobrepeso y 11,1% obesidad. En el primero se encontró una correlación entre el sobrepeso/obesidad y el consumo de bollería (p = 0,004). En las escuelas privadas se observó que los escolares de familias que habían utilizado el supermercado tenían un 26% menos de sobrepeso/ obesidad que los niños en edad escolar que no utilizaron este punto de venta de alimentos (p = 0,003). En el momento del estudio existe una asociación entre el uso de algunos tipos de punto de venta de alimentos (supermercado y panadería) y la prevalencia de sobrepeso/obesidad en escolares.


Subject(s)
DNA, Fungal/chemistry , HSP90 Heat-Shock Proteins/metabolism , Nucleic Acid Conformation , Saccharomyces cerevisiae , Saccharomyces cerevisiae Proteins/metabolism , Telomere/chemistry , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Chromosomal Proteins, Non-Histone/genetics , Chromosomal Proteins, Non-Histone/metabolism , DNA, Fungal/metabolism , Enzyme Activation , HSP90 Heat-Shock Proteins/genetics , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Telomerase/metabolism , Telomere-Binding Proteins/genetics , Telomere-Binding Proteins/metabolism , Telomere/metabolism
20.
Dental press j. orthod. (Impr.) ; 20(1): 45-51, Jan-Feb/2015. tab, graf
Article in English | LILACS | ID: lil-741446

ABSTRACT

INTRODUCTION: The consensus about the relationship between TMD and orthodontic treatment has gone from a cause and effect association between TMD and orthodontic treatment to the idea that there is no reliable evidence supporting this statement. OBJECTIVE: To assess the beliefs, despite scientific evidence, of Brazilian orthodontists about the relationship between TMD and orthodontic treatment with regards to treatment, prevention and etiology of TMD. METHODS: A survey about the relationship between TMD and orthodontic treatment was prepared and sent to Brazilian orthodontists by e-mail and social networks. Answers were treated by means of descriptive statistics and strong associations between variables were assessed by qui-square test. RESULTS: The majority of orthodontists believe that orthodontic treatment not only is not the best treatment option for TMD, but also is not able to prevent TMD. Nevertheless, the majority of orthodontists believe that orthodontic treatment can cause TMD symptoms. CONCLUSION: This study suggests that orthodontists' beliefs about the relationship between orthodontic treatment and TMD are in accordance with scientific evidence only when referring to treatment and prevention of TMD. The majority of orthodontists believe that, despite scientific evidence, orthodontic treatment can cause TMD. .


INTRODUÇÃO: o consenso sobre a relação entre DTM e tratamento ortodôntico foi de uma associação de causa e efeito à ideia de que não há evidências confiáveis que suportem essa afirmação. OBJETIVO: avaliar as crenças, sem considerar as evidências, de ortodontistas brasileiros sobre a relação entre DTM e tratamento ortodôntico com relação ao tratamento, prevenção e etiologia da DTM. MÉTODOS: um questionário sobre a relação entre DTM e tratamento ortodôntico foi preparado e enviado a ortodontistas brasileiros por meio de e-mail e mídias sociais. As respostas foram analisadas por estatística descritiva, e fortes associações entre as variáveis foram verificadas pelo teste χ2. RESULTADOS: a maioria dos ortodontistas acredita que o tratamento ortodôntico não é o melhor tratamento para DTM. Além disso, acreditam que não é a melhor forma para sua prevenção. Também, a maioria dos ortodontistas acredita que o tratamento ortodôntico pode causar sintomas de DTM. CONCLUSÃO: este estudo sugere que as crenças dos ortodontistas sobre a relação entre tratamento ortodôntico e DTM estão de acordo com as evidências científicas apenas quando se trata do tratamento e da prevenção de DTM. A maioria dos ortodontistas acredita que, apesar das evidências científicas, o tratamento ortodôntico pode causar DTM. .


Subject(s)
Humans , Cell Cycle Proteins/metabolism , DNA Replication/genetics , Forkhead Transcription Factors/metabolism , G1 Phase/physiology , Gene Expression Regulation/genetics , Protein Serine-Threonine Kinases/metabolism , Replication Origin/genetics , Signal Transduction/genetics , Blotting, Western , Cell Fractionation , Cell Line , Cell Cycle Proteins/genetics , /metabolism , DNA Primers/genetics , Fluorescent Antibody Technique , Forkhead Transcription Factors/genetics , Immunoblotting , Immunoprecipitation , Intercellular Signaling Peptides and Proteins/metabolism , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins c-myc/metabolism , Reverse Transcriptase Polymerase Chain Reaction , RNA Interference
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