miR-205 promotes proliferation and invasion of laryngeal squamous cell carcinoma by suppressing CDK2AP1 expression

BACKGROUND: The aberrant expression of microRNAs (miRNAs) has been found in various types of cancer. miR-205 was reported to be upregulated in laryngeal squamous cell carcinoma (LSCC) tissues, however, the mechanisms by which miR-205 functions as a regulator of LSCC are largely unknown. RESULTS: In this study, Real-time qPCR and Western blot assay showed that expression of miR-205 was upregulated and expression of cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) was downregulated in LSCC tissues. The expression levels of miR-205 were negatively related to those of CDK2AP1 in LSCC tissues and cell lines. Moreover, we found that miR-205 was the upstream regulator of CDK2AP1 and could suppress the CDK2AP1 expression in LSCC cells. 3-(4,5-dimethylthiazal-2-yl)-2,5-diphenyl-tetrazolium bromide assays and transwell invasion assay were performed to test the proliferation and invasion of LSCC cells. Gelatin zymography was used to detect the activity of MMP2 and MMP9. CDK2AP1, c-Myc and CyclinD1 expression in cells was assessed with Western blotting. We found that miR-205 was the upstream regulator of CDK2AP1 and could suppress the expression of CDK2AP1 in LSCC cells. In addition, miR-205 significantly induced cell proliferation and invasion by suppressing CDK2AP1 expression. Consistent with miR-205 inhibitors, overexpressed CDK2AP1 suppressed the activity of MMP2 and MMP9 and c-Myc and CyclinD1 expression in LSCC cells. CONCLUSION: These findings help us to better elucidate the molecular mechanisms of LSCC progression and provide a new theoretical basis to further investigate miR-205 as a potential biomarker and a promising approach for LSCC treatment.

Sinaptogénesis y esquizofrenia: rol de la proteína DISC 1 / Synaptogenesis and Schizophrenia: The role of DISC 1 protein

El presente trabajo aporta información respecto del posible rol en la esquizofrenia del gen DISC 1 y la proteína que este gen codifica. Se realiza un recorrido desde el hallazgo de la translocación cromosómica que llevó a su descubrimiento, hasta la perspectiva actual, que lo conceptualiza como un modulador funcional complejo. La mencionada translocación fue originariamente identificada en una familia escocesa, y se observó que cosegregaba con esquizofrenia y otros trastornos mentales. Actualmente, se considera a DISC 1 como una proteína central dentro de una red de interacciones con otras proteínas - lo que en varios trabajos se denomina interactoma -, tales como NDEL 1, LIS 1 y PDE 4B, entre otras.

This paper provides information regarding the possible role in schizophrenia of the DISC 1 gene and the protein it encodes. It is a tour from the discovery of the chromosomal translocation that led to its discovery, up to the current perspective, which is conceptualized as a complex functional modulator. The above translocation was originally identified in a Scottish family, and it was noted that it cosegregated with schizophrenia and other mental discorders. Currently, DISC 1 is considered as a central protein within its network of protein interactions (named as interactome in several papers), such as NDEL 1, LIS 1 and PDE 4B, among others.

Presença da mutação Arg337His do supressor tumoral P53 e mapa de deleção do cromossomo 17 em crianças e adultos com tumores adrenocorticais / Presence of the mutation Arg337His of the tumor suppressor P53 and deletion mapping of chromosome 17 in children and adults with adrenocorticol tumors

A mutação germinativa, Arg337His, do gene supressor tumoral p53 foi pesquisada em 71 pacientes brasileiros portadores de tumores adrenocorticais isolados. Análise de segregação evidenciou um mesmo haplótipo, associado à mutação Arg337His, configurando efeito fundador para esta mutação. Mapa de deleção para o cromossomo 17 demonstrou uma elevada freqüência 17/29 (59por cento), de perda completa deste cromossomo tanto em tumores benignos quanto malignos mostrando que não há correlação entre perda do cromossomo 17 e agressividade tumoral nestes pacientes. Instabilidade cromossômica envolvendo os cromossomos 2, 9 e 11 foi verificada nos pacientes que perderam o cromossomo 17. Perda de 3 ou mais cromossomos pode contribuir para o diagnóstico de malignidade nos tumores adrenocorticais / The Arg337His mutation of the P53 tumor suppressor was investigated in 71 Brazilian patients with isolated adrenocortical tumors. Segregation analysis evidenced the same haplotype, associated with Arg337His mutation, indicating a founder effect. Deletion mapping for chromosome 17 demonstrated a high frequency 17/29 (59 per cent) of chromosomal loss in both, benign and malignant tumors, without correlation between loss of chromosome 17 and tumor behavior. Chromosomal instability, involving chromosomes 2, 9 and 11 was verified in patients that had loss of chromosome 17. The concomitant loss involving of 3 or more chromosomes can contribute for diagnosis of malignancy in adrenocortical tumors...

Mutación puntual del gen supresor de tumores TP53 en lesiones preneoplásicas y neoplásicas del estómago / Mutations of TP53 suppressor gene in pre-neoplastic and neoplastic lesions of the stomach: cross-sectional study in a high risk region

Background: In the current model for the development of gastric cancer, regions of multifocal atrophic gastritis give rise to intestinal metaplasia, dysplasia and finally, adenocarcinoma. Aim: To study the frequency and characteristics of TP53 gene mutations in preneoplastic and neoplastic lesions of the stomach. Material and methods: DNA sequencing of the TP53 gene was performed in 46 patients with gastric carcinoma. Normal mucosa, intestinal metaplasia and invasive adenocarcinoma tissues were obtained by scraping 6-Ám histological sections from formalin-fixed and paraffin-embedded tissue. Results: DNA sequencing of exons 5-9 of the TP53 gene demonstrated a mutation in 31 percent of patients. These findings were seen both in tumoral tissue (13 cases) and in intestinal metaplasia (2 cases). Most mutations were found in exons 5 and 8, and the majority of them were transitions (10 out of 19 mutations). Discussion: Patients with gastric cancer showed a frequency of TP53 mutations similar to that previously communicated in populations with low gastric cancer risk. Moreover, there was a predominance of transitions, genetic alterations that are identified with carcinogenesis associated with N-nitrosamine compounds. Finally, mutations of TP53 gene were detected in areas of intestinal metaplasia

Patología molecular del cáncer pulmonar y sus lesiones precursoras: parte I, patología molecular del cáncer pulmonar / Molecular pathology of lung cancer and its precursor lesions: part I molecular pathology of lung cancer

En las últimas décadas se ha producido un gran avance en el conocimiento de las alteraciones moleculares que participan en la patogenia del cáncer pulmonar. Se ha determinado que esta neoplasia es el producto de un gran número de alteraciones genéticas (estimulando entre 10 y 20) que afectarían a oncogenes recesivos y a genes supresores de tumores. Además, se han establecido patrones de alteraciones genéticas en los diferentes tipos clínico-patológicos de cáncer pulmonar. Este conocimiento se ha aplicado al estudio de las alteraciones genéticas que participan en la progresión de las lesiones precursoras de esta neoplasia y al de sarrollo de métodos de detección precoz y control de pacientes con lesiones precursoras de cáncer pulmonar

Mutación del gen p53 en el cáncer de la vesícula biliar / P53 gene mutation in gallbladder cancer

Background: Gallbladder cancer frequency and mortality renders it one of the most important neoplastic diseases in Chile. P53 tumor suppressor gene has been studied in most types of cancer, but there is scarce information about it in gallbladder cancer. Aim: To study the frequency of P53 gene mutation in gallbladder cancer in the ninth region of Chile. Material and methods: In 25 pathological samples of gallbladder cancer, the direct amplification and sequencing of p53 gene exons 5,6,7,8-8 was possible. Results: Seventeen punctual mutations were observed in 13 cases (52 percent). There were 10 transitions, 5 transversions, one insertion (codon 194) and one deletion (codon 186). Eight cases had mutations in exon 5, six had mutations in exon 6, two had mutations in exon 7 and one had mutations in exons 8-9. In 14 of 25 cases, gene p53 protein was positive. When immunohistochemical expression of gene p53 protein was positive in more than 20 percent of cells, there was a high correlation between genetic alterations and immunohistochemical expression of the protein, with a specificity, sensitivity, positive and negative predictive values over 80 percent. Conclusions: P53 gene mutation is observed in a high proportion of gallbladder cancers at it can be accurately detected with conventional immunohistochemical techniques. The importance of this gene in the genesis of this carcinoma should be determined studying preneoplastic lesions and early carcinomas

Mutaciones del gen supresor de tumor p53 en adenocarcinoma gástrico / Mutations of p53 suppressor gene in gastric adenocarcinoma

Background: We have shown numeric alterations such as hyperploidy and hypoploidy with loss of chromosome 17 in primary gastric cancer. This chromosome maps p53 suppressor gene that induces the transcription of genes related to cellular cycle control, DNA synthesis and repair, cellular differentiation and apoptosis. Aim: To analyze, at a molecular level, the possible alterations of p53 suppressor gene in samples of gastric cancer and non tumoral mucosa. Material and methods: Tissue samples of gastric carcinoma and non tumoral gastric mucosa coming from 26 patients subjected to a total gastrectomy were analyzed. The mutation of p53 suppressor gene exons 7 to 9 were determined using a conformational polymorphism analysis in single strands of the gene and indirect sequencing in some cases. Results: Alterations in p53 gene were found in 77 percent of tumoral and 19 percent of non tumoral samples. T insertions in codons 260, 317 and 321, G insertion in codon 328 and G-T transvertion in codon 302 were found. Aminoacid sequence analysis of p53 protein obtained with sequencing data showed that T insertion in codon 260 could translate three erroneous aminoacids after the mutation and produce a truncated protein due to the creation of a stop codon. No associations between alterations of p53 gene and clinical or pathological variables such as age, sex, tumor localization, histological type and presence of Iymph node metastases were observed