CircRNAs: promising factors for regulating angiogenesis in colorectal cancer

Colorectal cancer (CRC) is one of the most common cancers in the world. The incidence rate of cancer is high. The overall response to traditional treatment methods such as surgery, radiotherapy, and chemotherapy is not very satisfactory. Therefore, finding new therapeutic targets is very important for improving CRC treatment. In recent reports, the role of circRNAs in regulating colorectal angiogenesis has been gradually revealed. CircRNAs can indirectly act on angiogenesis pathways and regulate the expression of growth factors such as vascular endothelial growth factor (VEGF). CircRNAs are endogenous noncoding RNAs formed by pre-mRNAs through exon circular splicing. The covalent closed-loop structure makes these RNAs highly conserved and stable. CircRNAs have been found in human plasma, serum, urine, and other body fluids. Their highly conserved characteristics play important roles in many biological activities. CircRNAs can participate in the progression of many diseases by sponging miRNAs, interacting with proteins, and regulating transcription. Angiogenesis can provide nutrients and oxygen for tumour proliferation and metastasis. Angiogenesis is an important sign of the formation of the tumour microenvironment. Here, we will summarize the role of the latest circRNAs in the mechanism of angiogenesis in CRC and provide potential therapeutic targets for clinical treatment. (AU)

Regulación del splicing alternativo: Implicaciones en el diagnóstico y tratamiento del cáncer / Alternative splicing regulation: Implications in cancer diagnosis and treatment

La expresión de la información genética es regulada por procesos como el splicing del ARN mensajero, mecanismo propuesto por Phil Sharp y Richard Roberts, quienes demostraron la existencia de secuencias intrónicas, las cuales interrumpen a la mayoría de los genes estructurales en eucariotes y deben ser removidas con gran precisión. Dicha remoción de intrones se denomina splicing, y permite generar variantes proteicas a partir de un solo gen, cada una con funciones diversas y, a menudo, antagónicas. Actualmente se sabe que el splicing es la principal fuente de diversidad proteica, ya que el 70% de los genes humanos lo sufren, y defectos en este proceso originan hasta el 50% de las enfermedades genéticas, incluido el cáncer. Cuando estos defectos se presentan en genes involucrados en adhesión, proliferación y ciclo celular, repercuten en la progresión de procesos cancerosos cuyo diagnóstico, tratamiento y prognosis puede determinarse en base a su perfil de splicing (AU)

The accurate expression of the genetic information is regulated by processes like mRNA splicing, proposed after the discoveries of Phil Sharp and Richard Roberts, who demonstrated the existence of intronic sequences, present in almost every structural eukaryotic gene, which should be precisely removed. This intron removal is called “splicing”, which generates different proteins from a single mRNA, with different or even antagonistic functions. We currently know that alternative splicing is the most important source of protein diversity, given that 70% of the human genes undergo splicing and that mutations causing defects in this process could originate up to 50% of genetic diseases, including cancer. When these defects occur in genes involved in cell adhesion, proliferation and cell cycle regulation, there is an impact on cancer progression, rising the opportunity to diagnose and treat some types of cancer according to a particular splicing profile (AU)

Mutaciones de Splicing / Splicing Mutations

El splicing o maduración del pre-mRNA es un mecanismo que está adquiriendo gran relevancia no sólo por las posibilidades que ofrece de expansión del proteoma, sino también por su implicación en la patofisiología de las enfermedades humanas. Las mutaciones de splicing alteran el procesamiento del mRNA al afectar a las secuencias del pre-mRNA (mutaciones en cis) o a las proteínas que intervienen en el splicing (mutaciones en trans). Las secuencias que pueden verse alteradas son: las limitantes de exones e intrones, la zona de ramificación, la zona rica en pirimidinas y también otros elementos reguladores que incrementan o suprimen la selección de un exón. La comprensión en profundidad del efecto de las mutaciones sobre el splicing puede abrir la puerta a su tratamiento mediante terapia moléculas (AU)

Splicing or maturation of pre-mRNA is a mechanism that is becoming more relevant not only for its potential expansion of the proteome, but also for its involvement in the physiopathology of human diseases. Splicing mutations after the processing of mRNA by affecting pre-mRNA sequences (mutations in cis) or proteins involved in splicing (mutations in trans). The sequences that can be altered are: the limiting areas between exons and interns, the branch site, the polypirimidine tract and, finally, other regulatory elements that enhance or suppress the selection of an exon. The whole understanding of the effect of mutations on the splicing processes will help to design molecular therapy targets to correct these defects (AU)

Envoltura nuclear, laminopatías y envejecimiento acelerado / Nuclear envelope, laminopathies and accelerated ageing

El síndrome de Hutchinson-Gilford es un síndrome progeroide que se caracteriza por un envejecimiento acelerado que comienza tempranamente en la infancia. El estudio de células de pacientes y el desarrollo de modelos animales (Zmpste24­/­, Zmpste24­/­Lmna+/­, LmnaLCO/LCO) que reproducen esta dolencia ha aportado nuevos conocimientos para entender las bases genéticas de esta enfermedad y así también profundizar en las del envejecimiento fisiológico. El fenotipo característico de este síndrome se debe a alteraciones en la lamina nuclear, estructura formada por un conjunto de filamentos intermedios (laminas A, B y C) que permiten mantener la organización de la envoltura nuclear. Se ha demostrado que una mutación del gen LMNA, que sintetiza la lamina A, es la del depósito de lamina A farnesilada (progerina) que es la causante de las alteraciones en la envoltura nuclear y del fenotipo de este raro síndrome. El empleo de moléculas que actúan sobre diferentes pasos en la síntesis de progerina se está revelando como un futuro terapéutico prometedor para revertir los efectos nocivos de su síntesis

Hutchinson-Gilford disease is a progeroid syndrome characterized by accelerated ageing beginning in early childhood. Study of several types of cells from patients with this syndrome and the development of animal models (Zmpste24­/­, Zmpste24­/­Lmna+/­, LmnaLCO/LCO) that mimic this disease have increased knowledge of the genetic foundations of this rare entity and those of normal ageing. The phenotypic features of this syndrome are caused by alterations in the fibrillar components of the nuclear lamina (lamins A, B, and C), which maintain the structure of the nuclear envelope. A point mutation in the gene for lamin A (LMNA) induces deposit of a farnesylated lamin A (progerin), which causes the nuclear alterations observed in the affected cells. The use of several molecules that interfere with progerin synthesis has been proposed as a promising potential therapeutic approach to reverse the adverse effects of progerin synthesis

Proapoptotic role of novel gene-expression factors

The mechanisms that control cellular proliferation, as well as those related with programmed cell death or apoptosis, require precise regulation systems to prevent diseases such as cancer. Events related to cellular proliferation as well as those associated with apoptosis involve the regulation of gene expression carried out by three basic genetic expression regulation mechanisms: transcription, splicing of the primary transcript for mature mRNA formation, and RNA translation, a ribosomal machinery-dependent process for protein synthesis. While development of each one of these processes requires energy for recognition and assembly of a number of molecular complexes, it has been reported that an increased expression of several members of these protein complexes promotes apoptosis in distinct cell types. The question of how these factors interact with other proteins in order to incorporate themselves into the different transduction cascades and stimulate the development of programmed cell death, although nowadays actively studied, is still waiting for a clear-cut answer. This review focuses on the interactions established between different families of transcription, elongation, translation and splicing factors associated to the progression of apoptosis (AU)

Los priones y su biología / Prions and their biology

Las prionopatías o encefalopatías espongiformes transmisibles son un conjunto de neurodegeneraciones letales de mamíferos cuyo denominador común es el metabolismo aberrante de una glicoproteína celular de membrana, denominada proteína del prion (PrP-C). Esta proteína, implicada hipotéticamente en la homeostasis del Cu (II) y candidata a desempeñar un papel activo en procesos de señalización y de adhesión celular, en condiciones patológicas se transforma en un isómero conformacional (PrP*, PrP-res, PrP-Sc, PrP-enfermedad de Creutzfeldt-Jakob, etc.). Este último, además de presentar propiedades bioquímicas divergentes, exhibe la propiedad novel de reconocer a la forma normal y transformarla en su homólogo en un proceso en el cual se postula la participación de factores aún no identificados (AU)