RESUMO
Lung cancer as the leading cause of cancer-related deaths can be initiated and progressed by the interaction between dynamically genetic and epigenetic elements, although mechanisms mediating lung cancer development and progression remain unclear. Tumor progenitor genes may contribute to lung carcinogenesis and cancer progression, are epigenetically disrupted at the early stages of malignancies even before mutations, and alter cell differentiation throughout tumor evolution. The present review explores potential roles and mechanisms of epigenetic modulators, modifiers and mediators in the development of lung cancer. We also overviewed potential mechanisms by which epigenetic modulators, modifiers and mediators control and regulate 3D nuclear architectures, and discussed translational efforts to epigenetic modifications for treatment of lung cancer. Deep understanding of epigenetic modulators, modifiers and mediators will benefit the discovery and development of new diagnostics and therapies for lung cancer.
Assuntos
Carcinogênese/genética , Metilação de DNA/genética , Epigênese Genética , Neoplasias Pulmonares/genética , Regulação Neoplásica da Expressão Gênica , Terapia Genética , Histonas/genética , Humanos , Neoplasias Pulmonares/patologia , MutaçãoRESUMO
Mitochondrial dysfunction has historically been linked to the cessation of cell function and ageing. Downstream effects such as reduced calcium buffering capacity, elevated levels of reactive oxygen species, and alterations in adenosine-5'-triphosphate are linked to a wide variety of pathological diseases. The importance of the mitochondria has increasingly been highlighted due to its potential as a therapeutic target for drug intervention and cell elimination in cancer. In addition, due to its origin, drugs targeting bacteria are required to be thoroughly tested prior to administration to prevent toxicity for the mitochondria. In this chapter, we will discuss a variety of factors that could influence mitochondrial dysfunction and highlight potential solutions to these. A comprehensive understanding regarding the mechanisms underlying mitochondrial dysfunction could aid in developing future therapeutic targets in multiple pathologies such as cancer and liver diseases.
Assuntos
Senescência Celular , Hepatopatias , Mitocôndrias Hepáticas , Neoplasias , Animais , Humanos , Hepatopatias/genética , Hepatopatias/metabolismo , Hepatopatias/patologia , Mitocôndrias Hepáticas/genética , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/patologia , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologiaAssuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Edição de Genes/ética , Acidaminococcus/genética , Proteínas de Bactérias/genética , Proteínas Associadas a CRISPR/genética , Sistemas CRISPR-Cas/genética , Endodesoxirribonucleases/genética , Edição de Genes/métodos , Genoma/genética , Humanos , Leptotrichia/genética , RNA Guia de Cinetoplastídeos/genéticaRESUMO
YABBY transcription factors (TFs) are plant-specific and are characterized by a C2-C2 zinc finger domain at the N-terminus and a YABBY domain at the C-terminus. In this study, eight YABBY genes were identified in the Brachypodium distachyon genome and were unevenly distributed across four chromosomes. Phylogenetic analysis classified BdYABBYs into FIL/YAB3, YAB2, CRC, and INO clades. Sixty-two putative cis-elements were identified in BdYABBY gene putative promoters, among them, CAAT-box, TATA-box, MYB, MYC, ARE, and Box_4 were shared by all. BdYABBY genes are highly expressed in inflorescences, and abiotic stresses regulate their expression. In addition, three transcripts of BdDL were identified. Over-expression in Arabidopsis has shown their different functions in reproductive development, as well as in response to cold stress. Our study lays the foundation for the functional elucidation of BdYABBY genes.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Brachypodium , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Brachypodium/genética , Brachypodium/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
As one kind of plant-specific transcription factors (TFs), WOX (Wuschel-related homeobox) plays an essential role in plant growth and development. In this study, 21 WOX TFs were identified in Brachypodium distachyon. They were divided into ancient, intermediate, and WUS clades based on phylogenetic analysis. These 21 BdWOX genes are mapped on 5 chromosomes unevenly. In the promoters, the most abundant cis-elements are ABRE, TGACG-motif, and G-box. qRT-PCR results showed that most BdWOX genes are expressed in vegetative and reproductive organs. Meanwhile, the expression of 14, 12, and 15 BdWOX genes are up-regulated by exogenous 6-BA, NAA, and GA, respectively. These results indicated that BdWOX genes participate in hormone signaling and regulate plant growth and development. Overexpression of BdWOX12 in Arabidopsis improved the root system, further indicating the functions of BdWOX genes in growth and development. This study provided a basis for the functional elucidation of BdWOX genes.