通过整合基因组不稳定性和免疫调节,TERT将端粒长度与癌症风险联系起来
Jingwei Zhao1,2, Jiayun Zhu1,2, Kangle Zhu3
1Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
Discover oncology
|September 30, 2025
概括
较长的端粒长度因果上增加了33种癌症的风险. TERT基因是关键的驱动因素,影响癌症的进展,并为诊断和治疗提供了潜力.
科学领域:
- 遗传学 遗传学 是一个
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 端粒稳态对于衰老和癌症至关重要,其消耗导致衰老和延长,使得癌细胞的无限增殖.
- 了解端粒长度与癌症风险之间的联系对于阐明瘤发生途径至关重要.
研究的目的:
- 调查端粒长度与胰腺癌易感性之间的因果关系.
- 为了确定分子通路和关键基因参与端粒驱动的癌症发育.
主要方法:
- 孟德尔随机化 (MR) 用于评估端粒长度对癌症风险的因果关系.
- 在SNPense分析中,确定了与端粒相关的基因,其次是基因本体学和KEGG通路丰富.
- 在TCGA数据集中分析了TERT表达,并使用ROC曲线评估了其诊断值.
主要成果:
- 增加端粒长度与33种癌症类型的更高风险显著相关.
- 确定了143个与端粒相关的基因,TERT是主要的枢纽基因.
- 在16种癌症中观察到TERT过度表达,显示出高的诊断潜力 (AUC>0.85).
结论:
- 端粒长度调节,特别是通过TERT轴,与癌症进展有关.
- 端粒功能障碍通过增加基因组不稳定性和改变免疫微环境来促进癌症.
- 这些发现支持TERT作为精确诊断和癌症治疗的目标.
相关概念视频
Replicative Cell Senescence
4.3K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.3K
Telomeres and Telomerase
26.9K
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
26.9K
Telomeres and Telomerase
7.0K
7.0K
Cancer Prevention
7.7K
Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
Some...
Some...
7.7K
Adaptive Mechanisms in Cancer Cells
7.0K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
7.0K
Non-LTR Retrotransposons
13.2K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
13.2K


