在结肠癌中PPARG激活的多omics探索:在调节区域内具有PPRE序列的激酶
Pritha Saha1, Palaniyandi Ravanan2, Priti Talwar3
1Apoptosis and Cell Survival Research Laboratory, 412G Pearl Research Park, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India.
Biology direct
|June 11, 2025
概括
这项研究揭示了PPARG在结肠癌细胞中调节的关键基因,为结肠直肠癌 (CRC) 提供了新的治疗点. 这些发现突出了PPARG的重点.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 癌症研究 癌症研究
背景情况:
- 过氧体增殖器激活受体 (PPAR),特别是PPAR-γ (PPARG),是调节细胞过程,如新陈代谢和亡的关键转录因子.
- PPARG是结直肠癌 (CRC) 的有希望的治疗标,是癌症死亡的主要原因,在零星的CRC病例中显著表现.
- 在CRC中PPARG的确切功能和监管网络仍然不完全理解,需要进一步阐明.
研究的目的:
- 研究PPARG在结直肠癌 (CRC) 细胞中的调控网络.
- 通过分析受PPARG激活影响的基因表达和结合位点来确定潜在的治疗点.
- 探索已识别的基因与CRC进展和患者存活率的相关性.
主要方法:
- 整合RNA-sequencing (RNA-seq) 和ChIP-sequencing (ChIP-seq) 数据在用罗西格利塔治疗的HT-29结肠癌细胞中.
- 对PPARG结合部位和差异表达基因 (DEGs) 响应治疗的分析.
- 基因本体学,通路丰富,蛋白质-蛋白质相互作用和miRNA分析以确定关键的调节基因和通路.
主要成果:
- 鉴定了14000至34000个PPARG结合位点和在罗西格利塔治疗后显著的基因表达差异 (43626780基因).
- 通过综合分析,解释了七个枢纽基因 (PTK2,HGS,CDK8,PRPF6,PRKDC,PRKCZ,MET),与CRC进展和患者存活率相关联.
- 使用独立数据集和CRISPR淘汰屏幕验证枢纽基因影响,通过疾病本体学和突变分析进一步影响各种癌症.
结论:
- 该研究阐明了PPARG在CRC中的监管网络,识别了具有预后价值的关键枢纽基因.
- 这些发现强调了PPARG作为CRC和相关癌症的治疗点的潜力.
- 为未来研究癌症治疗的PPARG介导途径建立了一个强大的框架.
相关概念视频
01:19Interactions Between Signaling Pathways
6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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...
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...
6.2K
01:22PI3K/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
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
02:07Tumor Progression
6.3K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.3K