Emerging Role of CRISPR/Cas9 Technology for MicroRNAs Editing in Cancer Research.

MicroRNAs (miRNA) are small, noncoding RNA molecules with a master role in the regulation of important tasks in different critical processes of cancer pathogenesis. Because there are different miRNAs implicated in all the stages of cancer, for example, functioning as oncogenes, this makes these small molecules suitable targets for cancer diagnosis and therapy. RNA-mediated interference has been one major approach for sequence-specific regulation of gene expression in eukaryotic organisms. Recently, the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system, first identified in bacteria and archaea as an adaptive immune response to invading genetic material, has been explored as a sequence-specific molecular tool for editing genomic sequences for basic research in life sciences and for therapeutic purposes. There is growing evidence that small noncoding RNAs, including miRNAs, can be targeted by the CRISPR/Cas9 system despite their lacking an open reading frame to evaluate functional loss. Thus, CRISPR/Cas9 technology represents a novel gene-editing strategy with compelling robustness, specificity, and stability for the modification of miRNA expression. Here, I summarize key features of current knowledge of genomic editing by CRISPR/Cas9 technology as a feasible strategy for globally interrogating miRNA gene function and miRNA-based therapeutic intervention. Alternative emerging strategies for nonviral delivery of CRISPR/Cas9 core components into human cells in a clinical context are also analyzed critically. Cancer Res; 77(24); 6812-7. ©2017 AACR.

Sexo Masculino e Hipertensão Arterial São Preditores de Placa à Angiotomografia das Coronárias / Male Gender and Arterial Hypertension are Plaque Predictors at Coronary Computed Tomography Angiography

Background: Systemic Arterial Hypertension (SAH) is one of the main risk factors for Coronary Artery Disease (CAD), in addition to male gender. Differences in coronary artery lesions between hypertensive and normotensive individuals of both genders at the Coronary Computed Tomography Angiography (CCTA) have not been clearly determined. Objective: To Investigate the calcium score (CS), CAD extent and characteristics of coronary plaques at CCTA in men and women with and without SAH. Methods: Prospective cross-sectional study of 509 patients undergoing CCTA for CAD diagnosis and risk stratification, from November 2011 to December 2012, at Instituto de Cardiologia Dante Pazzanese. Individuals were stratified according to gender and subdivided according to the presence (HT +) or absence (HT-) of SAH. Results: HT+ women were older (62.3 ± 10.2 vs 57.8 ± 12.8, p = 0.01). As for the assessment of CAD extent, the HT+ individuals of both genders had significant CAD, although multivessel disease is more frequent in HT + men. The regression analysis for significant CAD showed that age and male gender were the determinant factors of multivessel disease and CS ≥ 100. Plaque type analysis showed that SAH was a predictive risk factor for partially calcified plaques (OR = 3.9). Conclusion: Hypertensive men had multivessel disease more often than women. Male gender was a determinant factor of significant CAD, multivessel disease, CS ≥ 100 and calcified and partially calcified plaques, whereas SAH was predictive of partially calcified plaques. .

Fundamento: Doença Arterial Coronariana (DAC) tem como um dos principais fatores de risco a Hipertensão Arterial Sistêmica (HAS), além do sexo masculino. As diferenças nas lesões de artérias coronarianas entre hipertensos e normotensos de ambos os sexos pela Angiotomografia Computadorizada Coronariana (ATC) ainda não foram claramente determinadas. Objetivo: Investigar Escore de Cálcio (EC), extensão da DAC e as características de placas coronarianas à ATC em homens e mulheres com e sem HAS. Métodos: Estudo transversal prospectivo com 509 pacientes submetidos a ATC para diagnóstico e estratificação de risco de DAC, de novembro de 2011 a dezembro de 2012, no Instituto Dante Pazzanese de Cardiologia. Foram estratificados segundo o gênero e subdivididos de acordo com a presença (HT+) ou ausência (HT-) de HAS. Resultados: As mulheres HT+ apresentaram maior idade (62,3 ± 10,2 vs 57,8 ± 12,8, p = 0,01). Quanto à avaliação de extensão da DAC, os HT+ de ambos os sexos apresentaram DAC significativa, porém a doença multiarterial é mais frequente nos homens HT+. A análise da regressão para DAC significativa mostrou que idade e sexo masculino foram fatores determinantes de doença multiarterial e EC ≥ 100. Já a análise para os tipos de placas mostrou que a HAS se comportou como fator de risco preditor para placas parcialmente calcificadas (OR = 3,9). Conclusão: Homens hipertensos apresentaram mais frequentemente doença multiarterial. O sexo masculino foi fator determinante de DAC significativa, doença multiarterial, EC ≥ 100 e placas calcificadas e parcialmente calcificadas. Enquanto a HAS foi preditora de placas parcialmente calcificadas. .