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相关概念视频

Epigenetic Regulation01:37

Epigenetic Regulation

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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
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Abnormal Proliferation02:23

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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
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在早期前列腺癌和CTC中,DNA低甲基化使抗瘤免疫基因沉默

Hongshan Guo1, Joanna A Vuille2, Ben S Wittner2

  • 1Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

Cell
|June 16, 2023
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概括

早期的前列腺癌涉及DNA低甲基化, 在小鼠中重新激活这些基因阻止了瘤的生长,

关键词:
在CD1ADNA 低甲基化其他国家NKT 细胞循环中的瘤细胞免疫监测脂质抗原前列腺癌单细胞测序瘤发生

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科学领域:

  • 基因组表观遗传学
  • 癌症生物学
  • 免疫学

背景情况:

  • 癌症表现出DNA低甲基化,导致大染色体域中的基因沉默,但其在瘤发生中的作用尚不清楚.
  • 前列腺恶性瘤的进展包括表观遗传变化,包括DNA甲基化变化.

研究的目的:

  • 在前列腺癌中识别和描述早期DNA低甲基化域.
  • 研究这些低甲基化域在基因沉默和瘤发生中的作用.
  • 探索针对这些表观遗传变化的癌症治疗潜力.

主要方法:

  • 高分辨率,全基因组,单细胞DNA甲基化测序.
  • 从早期前列腺恶性瘤到转移性循环瘤细胞 (CTC) 的DNA甲基化模式的分析.
  • 在免疫能力较强的小鼠模型中进行基因表达分析和功能研究.

主要成果:

  • 从早期前列腺癌到转移性CTC均存在的40个核心低甲基化域.
  • 发现这些域内的沉默基因被丰富为免疫相关基因,包括CD1和干扰素诱导基因 (IFI16).
  • 在小鼠中证明重新表达CD1或IFI16的正确基因会废除瘤发生并激活抗瘤免疫力.

结论:

  • 早期的表观遗传变化,特别是DNA低甲基化域,通过沉默关键免疫基因显著塑造瘤发生.
  • 这些发现表明向特定的表观遗传变化可能是癌症免疫治疗的可行策略.
  • 低甲基化域在血液中可检测,通过CTC提供非侵入性癌症检测的潜力.