肝细胞母细胞瘤中的ADAM32瘤基因受IGF2BP2的调节
Takahiro Fukazawa1,2, Keiji Tanimoto3, Masato Kojima1,4
1Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima 734-8553, Japan.
Cancers
|June 13, 2025
概括
在肝细胞母细胞瘤中至关重要的瘤基因ADAM32在低氧条件下受到IGF2BP2的调节. 这一发现确定了IGF2BP2作为肝细胞母细胞瘤癌治疗的潜在治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 膜蛋白 a 解体和金属蛋白酶 (ADAMs) 涉及到各种人类癌症.
- ADAM32在肝细胞瘤 (HBL) 中显著过度表达,这有助于其致癌性质.
- ADAM32的调节机制,特别是在低氧状态下,在很大程度上仍未确定.
研究的目的:
- 在低氧条件下研究肝细胞瘤 (HBL) 中ADAM32表达的调节机制.
- 探索缺氧诱导因子 (HIF) 在调节ADAM32.2.中的潜在作用.
- 为了确定HBL治疗的新型分子标.
主要方法:
- 暴露HBL,乳腺癌和肺癌细胞系在低氧条件下 (1% O2).
- 分析ADAM32基因和蛋白质水平,以及促进剂活性.
- 微阵列分析以确定相关分子,包括m6A相关的蛋白质.
- 对HIF1A和IGF2BP2.2进行基因淘汰实验.
主要成果:
- 缺氧在HepG2,MCF7和MDA-MB-231细胞中增加了ADAM32水平,但在HUH-6或肺癌系中没有.
- 在低氧状态下,HepG2细胞中的ADAM32促进体活性保持不变,这表明后转录调节.
- IGF2BP2水平与ADAM32水平相关,并通过HIF1A敲击降低.
- 通过IGF2BP2的淘汰,ADAM32的表达减少,并减弱了其缺氧诱导.
结论:
- 致癌基因ADAM32是由IGF2BP2调节的,特别是在低氧压力下.
- IGF2BP2在ADAM32.2.的低毒性调节中起到关键的调解作用.
- IGF2BP2是一个有前途的分子标,用于开发HBL的新型抗癌疗法.
更多相关视频
07:59Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma
Published on: September 3, 2021
6.3K
08:50In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines
Published on: April 18, 2025
366
相关概念视频
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Abnormal Proliferation
4.5K
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...
4.5K
Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
The Retinoblastoma Gene
4.1K
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.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.1K
Negative Regulator Molecules
35.2K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.2K
