Respuesta de la línea celular de cáncer gástrico AGS al silenciamiento del ARN largo no codificante MALAT1
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Fecha
2022
Profesor/a Guía
Facultad/escuela
Idioma
es
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Universidad Andrés Bello
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Licencia CC
Licencia CC
Resumen
El cáncer gástrico (CG) es una de las enfermedades que más vidas cobra cada año a nivel
mundial, y la cual está afectando cada vez a más personas. A pesar de los avances en
investigación, medicina y tratamientos, los mecanismos moleculares que se ven involucrados en
el progreso y desarrollo de este cáncer todavía son desconocidos, y la supervivencia de los
pacientes en un plazo de 5 años sigue siendo insatisfactorio, especialmente si ya se ha alcanzado
el estado de metástasis. Diversos grupos de investigación han buscado explicar estos
mecanismos a través de los ARN no codificantes, moléculas con un largo mayor a 200 nucleótidos
que no se traducen ni codifican para proteínas, pero que se ha descubierto que cumplen roles
importantes en diversos procesos biológicos como diferenciación, proliferación, apoptosis y
autofagia. Se ha observado que varios ARN no codificantes largos tienen su expresión alterada
durante el desarrollo de distintos tipos de cáncer y, además participarían en su progresión. En
particular, el ARN no codificante largo MALAT-1 ha sido descrito en diferentes investigaciones,
siendo asociado a un diagnóstico desfavorable debido a un posible rol en el avance y progresión
del cáncer. A pesar de que existe información sobre este ARN en CG, esta es limitada, puntual o
contradictoria, lo que no permite dar una imagen global de las funciones que podría a estar
llevando a cabo este ARN largo no codificante. En esta investigación, nosotros buscamos
determinar que rol cumple MALAT-1 a nivel global en células de CG, hipotetizando que el
silenciamiento de MALAT1 en células de cáncer gástrico humanas AGS, produce cambios
transcripcionales globales y altera las propiedades de migración e invasión de estas
células.
En esta investigación nosotros encontramos que el silenciamiento del ARN largo no codificante
MALAT1 produce cambios transcripcionales globales, alterando de manera significativa la
expresión de 189 genes, entre los cuales 109 son regulados negativamente y 80 son regulados
positivamente. Entre los genes que llamaron nuestra atención, producto de participar en
mecanismos moleculares como la proliferación y migración celular, encontramos: MMP2,
SERPINE1 y 2, TNXB, FN1, entre otros. Según nuestros resultados, MALAT1 no alteraría la
capacidad de proliferación e invasión de las células de cáncer gástrico humanas AGS, pero sí
disminuye de manera significativa la capacidad de migración de estas células.
Gastric cancer (GC) is one of the diseases that claims more lives each year worldwide, and which is affecting more and more people. Despite advances in research, medicine and treatments, the molecular mechanisms involved in the progression and development of this cancer are still unknown, and patient survival within 5 years remains unsatisfactory, especially if metastasis has already been reached. Several research groups have sought to explain these mechanisms through non-coding RNAs, molecules longer than 200 nucleotides that are neither translated nor code for proteins, but have been found to play important roles in various biological processes such as differentiation, proliferation, apoptosis and autophagy. Several long non-coding RNAs have been observed to have altered expression during the development of different types of cancer and also to participate in its progression. In particular, the long non-coding RNA MALAT-1 has been described in different investigations, being associated with an unfavorable diagnosis due to a possible role in cancer progression. Although the information on this RNA exists in GC, it is limited, punctual or contradictory, which does not allow us to give a global picture of the functions that this long non-coding RNA could be carrying out. In this research, we sought to determine what role MALAT-1 plays globally in GC cells, hypothesizing that MALAT-1 silencing in human gastric cancer AGS cells produces global transcriptional changes and alters the migration and invasion properties of these cells. In this investigation we found that silencing of the long non-coding RNA MALAT-1 produces global transcriptional changes, significantly altering the expression of 189 genes, among which 109 are negatively regulated and 80 are positively regulated. Among the genes that caught our attention, due to their participation in molecular mechanisms such as cell proliferation and migration, we found: MMP2, SERPINE1 and 2, TNXB, FN1, among others. According to our results, MALAT-1 does not alter the proliferation and invasion capacity of AGS human gastric cancer cells, but it significantly decreases the migration capacity of these cells.
Gastric cancer (GC) is one of the diseases that claims more lives each year worldwide, and which is affecting more and more people. Despite advances in research, medicine and treatments, the molecular mechanisms involved in the progression and development of this cancer are still unknown, and patient survival within 5 years remains unsatisfactory, especially if metastasis has already been reached. Several research groups have sought to explain these mechanisms through non-coding RNAs, molecules longer than 200 nucleotides that are neither translated nor code for proteins, but have been found to play important roles in various biological processes such as differentiation, proliferation, apoptosis and autophagy. Several long non-coding RNAs have been observed to have altered expression during the development of different types of cancer and also to participate in its progression. In particular, the long non-coding RNA MALAT-1 has been described in different investigations, being associated with an unfavorable diagnosis due to a possible role in cancer progression. Although the information on this RNA exists in GC, it is limited, punctual or contradictory, which does not allow us to give a global picture of the functions that this long non-coding RNA could be carrying out. In this research, we sought to determine what role MALAT-1 plays globally in GC cells, hypothesizing that MALAT-1 silencing in human gastric cancer AGS cells produces global transcriptional changes and alters the migration and invasion properties of these cells. In this investigation we found that silencing of the long non-coding RNA MALAT-1 produces global transcriptional changes, significantly altering the expression of 189 genes, among which 109 are negatively regulated and 80 are positively regulated. Among the genes that caught our attention, due to their participation in molecular mechanisms such as cell proliferation and migration, we found: MMP2, SERPINE1 and 2, TNXB, FN1, among others. According to our results, MALAT-1 does not alter the proliferation and invasion capacity of AGS human gastric cancer cells, but it significantly decreases the migration capacity of these cells.
Notas
Memoria de título (Ingeniero en Biotecnología)
Esta Memoria de Título fue financiada por el proyecto ANID FONDECYT Iniciación 11200308 y el Proyecto Núcleo UNAB DI-03-22/NUC.
Esta Memoria de Título fue financiada por el proyecto ANID FONDECYT Iniciación 11200308 y el Proyecto Núcleo UNAB DI-03-22/NUC.
Palabras clave
Cáncer Gástrico, Investigaciones, ARN