RESUMO
Breast cancer is one of the most lethal malignancies in women in the world. Various factors are involved in the development and promotion of the malignancy; most of them involve changes in the expression of certain genes, such as microRNAs (miRNAs). MiRNAs can regulate signaling pathways negatively or positively, thereby affecting tumorigenesis and various aspects of cancer progression, particularly breast cancer. Besides, accumulating data demonstrated that miRNAs are a novel tool for prognosis and diagnosis of breast cancer patients. Herein, we will review the roles of these RNA molecules in several important signaling pathways, such as transforming growth factor, Wnt, Notch, nuclear factor-κ B, phosphoinositide-3-kinase/Akt, and extracellular-signal-regulated kinase/mitogen activated protein kinase signaling pathways in breast cancer.
Assuntos
Neoplasias da Mama/genética , Carcinogênese/genética , MicroRNAs/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Sistema de Sinalização das MAP Quinases/genética , NF-kappa B/genética , Fosfatidilinositol 3-Quinase/genética , Receptores Notch/genética , Transdução de Sinais/genética , Proteínas Wnt/genéticaRESUMO
Breast cancer is a major clinical challenge that affects a wide range of the female population and heavily burdens the health system. In the past few decades, attempts have been made to understand the etiology of breast cancer, possible environmental risk factors, and the genetic predispositions, pathogenesis, and molecular aberrations involved in the process. Studies have shown that breast cancer is a heterogeneous entity; each subtype has its specific set of aberrations in different cell signaling pathways, such as Notch, Wnt/ß-catenin, transforming growth factor-ß, and mitogen-activated protein kinase pathways. One novel group of molecules that have been shown to be inducted in the regulation of multiple cell signaling pathways is the long noncoding RNAs (lncRNAs). These molecules have important implications in the regulation of multiple signaling pathways by interacting with various genes, affecting the transcription process, and finally, playing roles in posttranslational control of these genes. There is growing evidence that lncRNAs are involved in the process of breast cancer formation by effecting the aforementioned signaling pathways, and that this involvement can have significant diagnostic and prognostic values in clinical contexts. The present review aims to elicit the significance of lncRNAs in the regulation of cell signaling pathways, and the resulting changes in cell survival, proliferation, and invasion, which are the hallmarks of breast cancer.
Assuntos
Neoplasias da Mama/genética , Proliferação de Células/genética , RNA Longo não Codificante/genética , Neoplasias da Mama/patologia , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , PrognósticoRESUMO
Mitogen-activated protein kinase (MAPK) signaling pathways organize a great constitution network that regulates several physiological processes, like cell growth, differentiation, and apoptotic cell death. Due to the crucial importance of this signaling pathway, dysregulation of the MAPK signaling cascades is involved in the pathogenesis of various human cancer types. Oxidative stress and DNA damage are two important factors which in common lead to carcinogenesis through dysregulation of this signaling pathway. Reactive oxygen species (ROS) are a common subproduct of oxidative energy metabolism and are considered to be a significant physiological modulator of several intracellular signaling pathways including the MAPK pathway. Studies demonstrated that the MAP kinases extracellular signal-regulated kinase (ERK) 1/2 and p38 were activated in response to oxidative stress. In addition, DNA damage is a partly common circumstance in cell life and may result in mutation, cancer, and even cell death. Recently, accumulating evidence illustrated that the MEK/ERK pathway is associated with the suitable performance of cellular DNA damage response (DDR), the main pathway of tumor suppression. During DDR, the MEK/ERK pathway is regularly activated, which contributes to the appropriate activation of DDR checkpoints to inhibit cell division. Therefore, the aim of this review is to comprehensively discuss the critical function of MAPK signaling in oxidative stress, DNA damage, and cancer progression.
RESUMO
FGF21 is a peptide hormone that regulates homeostasis of lipid and glucose as well as energy metabolism. It is mainly expressed and secreted in liver and adipose tissues, and it is expressed in lower amounts in the aorta. Recent clinical and preclinical studies indicate increased serum FGF21 levels in atherosclerosis patients. Also, FGF21 therapy has been reported to reduce the initiation and progression of atherosclerosis in animal models and in vitro studies. Moreover, growing evidence indicates that administration of exogenous FGF21 induces anti-atherosclerotic effects, because of its ability to reduce lipid profile, alleviation of oxidative stress, inflammation, and apoptosis. Therefore, FGF21 can not only be considered as a biomarker for predicting atherosclerosis, but also induce protective effects against atherosclerosis. Besides, serum levels of FGF21 increase in various diseases including in diabetes mellitus, hypertension, and obesity, which may be related to initiating and exacerbating atherosclerosis. On the other hand, FGF21 therapy significantly improves lipid profiles, and reduces vascular inflammation and oxidative stress in atherosclerosis related diseases. Therefore, further prospective studies are needed to clarify whether FGF21 can be used as a prognostic biomarker to identify individuals at future risk of atherosclerosis in these atherosclerosis-associated diseases. In this review, we will discuss the possible mechanism by which FGF21 protects against atherosclerosis.