通过PTEN/AKT/mTOR通路对多发性骨髓瘤的扩散和亡产生影响
Jing Zi-Zi1, Yu Wei1, Tang Jia-Lin1
1Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
循环素依赖激酶调节子单元2 (CKS2) 在多发性骨髓瘤中被上调,并驱动癌症的进展. 抑制CKS2会减少扩散并诱导细胞亡,将其确定为这种血液学疾病的潜在治疗标.
科学领域:
- 血液学 血液学 血液学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 多发性骨髓瘤 (MM) 是一种严重的血液性恶性瘤,其分子驱动因素尚未完全理解.
- 转录基因分析已经确定了循环素依赖激酶调节子单元2 (CKS2) 作为MM病原发生的潜在关键因素.
研究的目的:
- 研究CKS2在多发性骨髓瘤进展中的功能作用.
- 阐明CKS2参与MM的分子机制.
- 评估CKS2作为潜在的治疗点.
主要方法:
- 针对CKS2表达的RNA测序和临床样本分析.
- 使用MM细胞系 (MM.1S,RPMI-8226) 进行体外研究,以评估增殖和亡.
- 在体内异种移植小鼠模型和西部斑点分析.
- 生物信息分析,共免疫沉和共聚焦显微镜用于识别和验证CKS2互动体.
- 使用AlphaFold2.2.进行结构建模.
主要成果:
- CKS2 knockdown 抑制了MM细胞的增殖和诱导亡;CKS2过度表达促进了增殖和抑制了亡.
- 通过PTEN/AKT/mTOR信号通路,CKS2调节了增殖和亡.
- CKS2直接与硫素 (TXN) 相互作用,这调节了CKS2的稳定性.
结论:
- CKS2在调节多发性骨髓瘤细胞平衡中起着至关重要的作用.
- CKS2是多发性骨髓瘤的有希望的治疗点,需要进一步的临床前研究.
更多相关视频
07:48Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
Published on: December 26, 2016
07:24Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube SWCNT-delivered MALAT1 Antisense Oligos
Published on: December 13, 2018
相关概念视频
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Abnormal Proliferation
PI3K/mTOR/AKT Signaling Pathway
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Inhibition of Cdk Activity
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
