Video Experimental Relacionado

Updated: May 12, 2026

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

La retrotransposición endógena activa las vías oncogénicas en el carcinoma hepatocelular

Ruchi Shukla¹, Kyle R Upton, Martin Muñoz-Lopez

¹Division of Genetics and Genomics, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush EH25 9RG, UK.

|April 2, 2013

Resumen

Las retrotransposonas LINE-1 impulsan el cáncer de hígado (carcinoma hepatocelular) al interrumpir los genes supresores de tumores como los mutados en los cánceres colorrectales (MCC) y activar oncogenes como la supresión de la tumorigenicidad 18 (ST18). Estos elementos móviles son factores etiológicos clave en el desarrollo de HCC.

Área de la Ciencia:

Genética La genética.
Biología Molecular Biología Molecular
Oncología Oncología.

Sus antecedentes:

Las retrotransposones LINE-1 (L1) son elementos móviles abundantes en el genoma humano.
Las inserciones L1 pueden afectar la función genética y la enfermedad, pero su papel en el cáncer no se entiende completamente.

Objetivo del estudio:

Investigar los mecanismos por los cuales los retrotransposones L1 contribuyen a la tumorigénesis del carcinoma hepatocelular (CCH).
Para identificar eventos específicos mediados por L1 que conducen al cáncer de hígado.

Principales métodos:

Se utilizó la secuenciación mejorada de captura de retrotransposón (RC-seq) en 19 genomas de HCC.
Se realizaron ensayos experimentales para confirmar los impactos funcionales de las inserciones L1.

Principales resultados:

Se identificaron eventos de retrotransposición de la línea germinal L1 en el gen mutado en cáncer colorrectal (MCC) en el 21.1% de los pacientes con CHC, lo que condujo a la ablación de la expresión de MCC y la activación de la señalización Wnt.
Se descubrieron inserciones L1 específicas del tumor que activan la supresión de la tumorigenicidad 18 (ST18) al interrumpir un bucle de retroalimentación negativa.
Se observó una amplificación frecuente de ST18 en modelos de HCC de ratón, lo que respalda su papel como oncogén hepático.

Conclusiones:

La retrotransposición L1 es un factor etiológico significativo en el carcinoma hepatocelular.
Dos mecanismos distintos mediados por L1 contribuyen al desarrollo de HCC: la inactivación de los supresores tumorales y la activación de los oncogenes.

Más Videos Relacionados

A Hepatocellular Cancer Patient-Derived Organoid Xenograft Model to Investigate Impact of Liver Regeneration on Tumor Growth

A Hepatocellular Cancer Patient-Derived Organoid Xenograft Model to Investigate Impact of Liver Regeneration on Tumor Growth

Published on: February 2, 2024

Generation of Subcutaneous and Intrahepatic Human Hepatocellular Carcinoma Xenografts in Immunodeficient Mice

Generation of Subcutaneous and Intrahepatic Human Hepatocellular Carcinoma Xenografts in Immunodeficient Mice

Published on: September 25, 2013

Videos de Conceptos Relacionados

Mechanisms of Retrovirus-induced Cancers

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...

Mechanisms of Retrovirus-induced Cancers

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...

Non-LTR Retrotransposons

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...

Cancer-Critical Genes I: Proto-oncogenes

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...

Cancer-Critical Genes I: Proto-oncogenes

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...

Induced Pluripotent Stem Cells

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...