低NDRG2,由MYC/MIZ-1复合体和甲基化调节,预测DLBCL患者的不良结果
Shuang Wu1, Jie Zhang2,3, Shan Chen2,3
1Department of Hematology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, Jiangsu Province, China.
Annals of hematology
|June 6, 2024
概括
N-Myc下游调节基因2 (NDRG2) 通过抑制MYC和MIZ-1抑制扩散性大B细胞淋巴瘤 (DLBCL),影响细胞增殖和新陈代谢. 对于DLBCL患者来说,NDRG2和MYC是有希望的预后生物标志物.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症新陈代谢 癌症新陈代谢
背景情况:
- 扩散性大B细胞淋巴瘤 (DLBCL) 是最常见的非霍奇金淋巴瘤.
- N-Myc下游调节基因2 (NDRG2) 作为瘤抑制剂,在许多癌症中下调.
- 在DLBCL中代谢变化的机制仍然不完全理解.
研究的目的:
- 研究NDRG2,MYC和Myc相互作用的指蛋白1 (MIZ-1) 在DLBCL淋巴发育中的作用.
- 探索DLBCL中NDRG2,MYC和MIZ-1的调控机制和生物功能.
- 分析这些基因与细胞代谢的关联以及DLBCL的预后意义.
主要方法:
- 在DLBCL细胞系和人类瘤组织中分析NDRG2,MYC和MIZ-1的表达.
- 使用5-Aza-2'-deoxycytidine (5-Aza-CDR) 调查NDRG2甲基化及其逆转.
- 生物信息学分析和生存分析,以评估基因关联和预后价值.
主要成果:
- 在DLBCL细胞系和瘤组织中,NDRG2表达与MYC和MIZ-1相反相关.
- MYC和MIZ-1促进了DLBCL细胞的增殖,而NDRG2则诱导了亡.
- 通过5-Aza-CDR降低MYC和抑制DLBCL细胞存活的NDRG2甲基化逆转;MYC-NDRG2相互作用影响mTOR相关的能量代谢.
- NDRG2和MYC被确定为DLBCL患者的显著预后生物标志物.
结论:
- MYC/MIZ-1复合体与NDRG2相互作用,调节DLBCL细胞增殖和细胞亡.
- NDRG2,MYC和MIZ-1影响DLBCL代谢,并作为潜在的预后标志物.
- 针对NDRG2-MYC轴可能为DLBCL提供治疗策略.
相关概念视频
02:23Abnormal 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
01:46Epigenetic Regulation
31.0K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
31.0K
01:23Negative Regulator Molecules
35.3K
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.
35.3K
02:23Master Transcription Regulators
6.9K
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...
6.9K
01:15Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
03:03mTOR 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