由MEF2A转录激活的PSMD14通过升级SPON2表达来促进胰腺癌的发展
Yun-He Hao1, Cheng-Ru Yang1, Wu-Jiang Shi1
1Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
The Kaohsiung journal of medical sciences
|March 11, 2025
概括
蛋白质素26S亚单元非ATPase 14 (PSMD14) 通过通过RBM15B稳定SPON2 mRNA促进胰腺癌. 抑制PSMD14可减少瘤生长和转移,提供潜在的治疗点.
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:
- 蛋白质酶26S子单元非ATPase14 (PSMD14) 与各种癌症有关.
- 它在胰腺癌 (PC) 中的具体作用和机制尚不清楚.
研究的目的:
- 研究胰腺管腺癌 (PDAC) 中PSMD14的功能和分子机制.
主要方法:
- 分析PDAC组织,细胞增殖,迁移和入侵测定.
- 染色体免疫沉降 (ChIP),双化酶,RNA免疫沉降 (RIP),共同免疫沉降 (Co-IP) 和甲基化RNA免疫沉降 (MeRIP) 的测定.
- 在小鼠体内皮下和肺转移的模型.
主要成果:
- 在PDAC组织中,PSMD14被上调,其敲击抑制了PC细胞活力,增殖,迁移和入侵.
- MEF2A通过转录激活了PSMD14的表达,从而促进了RBM15B的脱泛化.
- 通过RBM15B介导的m6A修饰,PSMD14增强了SPON2的mRNA稳定性,SPON2的过度表达抵消了PSMD14的淘汰效应.
- 在体内,PSMD14敲击抑制了瘤生长和肺转移.
结论:
- 由MEF2A激活的PSMD14通过通过RBM15B介导的m6A修饰来向上调节SPON2表达来促进PC进展.
- 向PSMD14可能代表胰腺癌的新疗法策略.
相关概念视频
MAPK Signaling Cascades
5.1K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.1K
Abnormal Proliferation
4.4K
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...
4.4K
mTOR Signaling and Cancer Progression
3.7K
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...
3.7K
Master Transcription Regulators
6.8K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.8K
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
Induced Pluripotent Stem Cells
3.9K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
3.9K


