Drp1拼接变体调节卵巢癌线粒体动力学和瘤进展
Zaineb Javed1,2,3, Dong Hui Shin3,4, Weihua Pan1,2
1UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
EMBO reports
|August 27, 2024
概括
一种特定的变异的胺相关蛋白1 (Drp1) 裂变蛋白,缺少外因子16,通过改变线粒体动力学,促进卵巢癌的进展和化学抵抗. 针对这种拼接变体提供了一个潜在的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 分子瘤学分子瘤学
- 线粒体动力学的动力学
背景情况:
- 异常的线粒体裂变/融合动态与癌症病理有关.
- 与胺相关的蛋白1 (Drp1/DNM1L) 是线粒体分裂的关键调节者.
- Drp1转录的替代拼接为其在瘤细胞中的功能增加了复杂性.
研究的目的:
- 研究Drp1替代拼接变体在癌症中的作用.
- 确定在卵巢癌中缺乏16号外因子的Drp1变异的功能后果.
- 评估针对这种特定的Drp1拼接变异的治疗潜力.
主要方法:
- 在卵巢瘤中对Drp1替代拼接变体表达的分析.
- 使用细胞系和动物模型进行体外和体外研究.
- 利用小干扰RNAs (siRNAs) 专门针对缺少16号外因子的Drp1变体.
主要成果:
- 缺乏外因子16的Drp1的高表达与卵巢癌患者的预后不佳相关.
- 这种变异导致Drp1的错位化,导致线粒体融合,呼吸能力增强和亲瘤原生表型.
- 缺少16号外子会降低对化疗的敏感性,并且在对亡刺激的反应中取消裂变.
结论:
- Drp1替代拼接在癌症中起着关键的病理生理作用.
- 缺少16号外因子的Drp1变异驱动瘤进展和化疗抵抗.
- 准Drp1替代拼接是卵巢癌治疗的一个有希望的途径.
相关概念视频
RNA Splicing
56.2K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.2K
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
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
Alternative RNA Splicing
21.1K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.1K
PI3K/mTOR/AKT Signaling Pathway
3.4K
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...
3.4K
Tumor Progression
6.3K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.3K


