在乳腺癌中,ZC3H12D和DDX5对抗性调节环林D1mRNA稳定性和细胞周期进展
Liang Sun1, Xueting Liu2, Wenbao Lu2
1Department of Laboratory Medicine, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, China.
Cancer medicine
|November 20, 2025
概括
RNA结合蛋白ZC3H12D和DDX5在乳腺癌中充当细胞循环对手. ZC3H12D破坏了CCND1mRNA的稳定,而DDX5则稳定了它,影响了瘤的进展,并提供了控制癌症细胞周期的见解.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 基因规则 基因规则
背景情况:
- 癌症中不受控制的细胞循环进展源于细胞循环促进和抑制基因的失衡.
- 控制细胞周期基因表达的精确机制,特别是涉及RNA结合蛋白 (RBPs) 的机制,尚未完全理解.
研究的目的:
- 研究RBPs ZC3H12D和DDX5在乳腺癌中的作用.
- 阐明ZC3H12D和DDX5调节乳腺瘤细胞周期进展和整体瘤发育的分子机制.
主要方法:
- 在人类乳腺癌中RBP表达的生物信息分析.
- 在乳腺癌模型中对ZC3H12D和DDX5进行了体外和体内功能研究.
- 利用了包括RNA测序,irCLIP-Seq,RIP,光酶测定,mRNA稳定性测定和质谱等技术来确定分子机制.
主要成果:
- 乳腺癌组织中ZC3H12D表达减少,DDX5表达增加,与患者预后相关.
- ZC3H12D和DDX5相互控制了G1/S细胞周期过渡,影响了乳腺瘤的进展.
- ZC3H12D通过结合其3'UTR降解了CCND1mRNA,其中RPL4对这一过程至关重要;DDX5结合了CCND1mRNA,但提高了其稳定性.
结论:
- 在乳腺癌中,ZC3H12D和DDX5作为细胞循环对手.
- 这些RBP调节细胞循环促进基因的表达,为防止不受控制的癌细胞增殖提供了新的策略.
相关概念视频
02:34Inhibition of Cdk Activity
5.5K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K
02:39Positive Regulator Molecules
6.4K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
6.4K
01:45Positive Regulator Molecules
133.9K
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
133.9K
01:23Negative Regulator Molecules
38.2K
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.
38.2K
01:27Molecular Factors Affecting Cell Division
3.8K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.8K
00:50Anaphase Promoting Complex
3.3K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.3K