Uso de microRNAS como método diagnóstico para cáncer de colon
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2020
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Universidad Andrés Bello
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Licencia CC
Licencia CC
Resumen
En Chile, el cáncer colorrectal (CCR) es una patología que ha aumentado su incidencia y mortalidad en los últimos años. Actualmente su diagnóstico es realizado en base a métodos invasivos, costosos o poco confiables. En consecuencia, surge la necesidad de buscar nuevas alternativas para su detección temprana, donde los microRNAs (miRNAs) emergen como una opción viable como biomarcadores diagnósticos de CCR. Los microRNAs son pequeñas moléculas de RNA no codificantes capaces de regular indirectamente la expresión génica y pueden sufrir desregulaciones que en algunos casos promueven la proliferación celular y otros procesos que llevan a la transformación tumoral por sus actividades como oncogenes y/o supresores de tumores.
En esta investigación se analizaron 5 microRNAs (miR-21, miR-92a, miR-135b, miR-200c y miR-802) que podrían ser un posible blanco de estudio como nuevas herramientas en el diagnóstico del CCR, también se distinguieron factores que inciden sobre la estandarización de la medición de estos. Como resultado, obtuvimos que miR-21 con miR-92a podrían ser los más aptos para la detección temprana de CCR, pero no específicos de la patología al encontrarse desregulados en distintos cánceres e incluso en otras enfermedades.
En cuanto a miR-135b y miR-802 no se pudo llegar a discernir su utilidad clínica pues deben ser estudiados con mayor profundidad y enfoques.
Respecto a miR-200c, este fue descartado debido a su actividad contradictoria en CCR, falta de datos sobre su especificidad y sensibilidad y ser estudiado principalmente en cultivos celulares.
Además, evidenciamos que actualmente no existe una estandarización universal para la cuantificación de miRNAs que permitan la comparación y reproducibilidad entre estudios relacionados a ello. Complementario a lo anterior, se sugiere la búsqueda de nuevos microRNAs que sean específicos para CCR tomando en cuenta los factores que influyen en sus mediciones, como el tipo de muestra y extracción de RNA, entre otros.
Colorectal cancer (CCR) incidence and mortality has increased in Chile in the last few years. CCR diagnosis is normally performed using invasive and expensive methods yet with not total precision. As a consequence, searching for new early detection alternatives has become a must. At this point is where microRNAs (miRNAs) are considered as a viable and reliable option as CCR diagnostic biomarkers. MicroRNAs are small noncoding RNA molecules involved in gene expression regulation. In occasions miRNAs can be dysregulated themselves pathologically promoting cell proliferation and other processes that drive to tumorous cell transformation. miRNAs involved in these diseases are those with oncogene like or tumor suppressor activities. In this job, we focused on 5 microRNAs (miR-21, miR-92a, miR-135b, miR-200c and miR-802) that may be studied as new diagnostic tools in CCR diagnosis. In this study we also distinguished factors that may have an effect on the standardization of these miRNAs’ measurements. As a result, we conclude that both miR-21 and miR-92a might be the most suitable miRNas out of the five selected for early detection of CCR. However, they are not CCR specific because they are also dysregulated in other different cancers or even in other different diseases. In relation to miR-135b and miR-802 we could not reach any conclusion related to its clinical usefulness. More and deeper studies involving these two RNAs are needed. We finally discarded mir-200 as a diagnostic marker because there is contradictory data related to its role in CCR, a lack of knowledge about its specificity and sensitivity and because it has been studied mainly in cell culture lines In general terms we found that there are no clear standard rules about miRNA quantification that may allow to compare among different studies establishing reproducibility of the results. Moreover, we suggest that a search for new CCR specific miRNAs should be done taking into account the factors that influenc
Colorectal cancer (CCR) incidence and mortality has increased in Chile in the last few years. CCR diagnosis is normally performed using invasive and expensive methods yet with not total precision. As a consequence, searching for new early detection alternatives has become a must. At this point is where microRNAs (miRNAs) are considered as a viable and reliable option as CCR diagnostic biomarkers. MicroRNAs are small noncoding RNA molecules involved in gene expression regulation. In occasions miRNAs can be dysregulated themselves pathologically promoting cell proliferation and other processes that drive to tumorous cell transformation. miRNAs involved in these diseases are those with oncogene like or tumor suppressor activities. In this job, we focused on 5 microRNAs (miR-21, miR-92a, miR-135b, miR-200c and miR-802) that may be studied as new diagnostic tools in CCR diagnosis. In this study we also distinguished factors that may have an effect on the standardization of these miRNAs’ measurements. As a result, we conclude that both miR-21 and miR-92a might be the most suitable miRNas out of the five selected for early detection of CCR. However, they are not CCR specific because they are also dysregulated in other different cancers or even in other different diseases. In relation to miR-135b and miR-802 we could not reach any conclusion related to its clinical usefulness. More and deeper studies involving these two RNAs are needed. We finally discarded mir-200 as a diagnostic marker because there is contradictory data related to its role in CCR, a lack of knowledge about its specificity and sensitivity and because it has been studied mainly in cell culture lines In general terms we found that there are no clear standard rules about miRNA quantification that may allow to compare among different studies establishing reproducibility of the results. Moreover, we suggest that a search for new CCR specific miRNAs should be done taking into account the factors that influenc
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Tesis (Tecnología Médica)
Palabras clave
Cáncer Colorrectal, Diagnóstico Genético, Indice de Mortalidad, Prevención y Control de Enfermedades, Chile