癌症光热-铁死亡-化疗协同治疗比较的RNA-seq数据
收藏国家青藏高原科学数据中心2023-02-13 更新2024-03-06 收录
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Ferroptosis 是最近发现的程序性细胞死亡,由细胞亚铁离子爆发和随后的 Fenton 反应引起。 由于严格控制铁代谢,肿瘤细胞中的铁源是有限的。 由于在铁死亡癌症治疗中很少考虑分层铁结构,多层 Fe2O3 结构 (UF@PPDF NPs) 是通过调制超小 γ-Fe2O3 纳米晶体组件,并进一步结合癌细胞靶向叶酸 (FA)、化疗药物多柔比星 ( 多克斯)。 分层组装的 γ-Fe2O3 纳米晶体有助于可切换的磁共振成像 (MRI)、大大提高的铁死亡效率和非常高的二次近红外 (NIR-II) 光热转换。 对于 MRI,UF@PPDF 纳米粒子 (NPs) 可以在尺寸和紧凑度方面清晰地显示组织,并具有动态 T2-T1 成像切换。 UF@PPDF NPs 在 NIR-II 照射下表现出高效的光热疗法 (PTT),以及铁离子和 Dox 的受控释放,从而实现 PTT-化疗-铁死亡三功能协同癌症治疗,用于肿瘤消融。 差异表达基因的 RNA 测序分析表明这种疗法在癌细胞信号传导中具有多方面的作用。 细胞呼吸和电子传递显着上调,而包括染色质修饰和 RNA 转录活性在内的表观遗传途径被严重下调,具有细胞凋亡的总体影响。 因此,γ-Fe2O3 结构为高效深部肿瘤治疗提供了新的可能性。将HeLa细胞用PBS和UF@PPDF NPs和 NIR-II 1064 nm激光照射(1.1 W cm−2, 10 分钟)。之后,将细胞连续培养2小时用于RNA 测序。数据质量进行质控,数据使用 Trimmomatics v0.38 进行了预处理。然后使用 HISAT v2.1.0将读数比对到hg38基因组。FPKM由Rsubread和edgeR计算得出。富集倍数变化和p值由edgeR及其负二项式模型量化。
Ferroptosis is a recently discovered form of programmed cell death, triggered by cellular ferrous ion burst and subsequent Fenton reaction. Iron metabolism is tightly regulated, leading to limited iron sources in tumor cells. Since stratified iron-based nanostructures are rarely considered in ferroptosis-based cancer therapy, multilayer Fe₂O₃-based assemblies (UF@PPDF NPs) were fabricated by modulating the assembly of ultrasmall γ-Fe₂O₃ nanocrystals, followed by conjugation with cancer cell-targeting folic acid (FA) and the chemotherapeutic drug doxorubicin (Dox). The hierarchically assembled γ-Fe₂O₃ nanocrystals enable switchable magnetic resonance imaging (MRI), greatly enhanced ferroptosis efficiency, and exceptionally high second near-infrared (NIR-II) photothermal conversion performance. For MRI, UF@PPDF NPs can clearly visualize tissues in terms of size and compactness, with dynamic T2-T1 imaging switching. UF@PPDF NPs exhibit efficient photothermal therapy (PTT) under NIR-II irradiation, alongside controlled release of ferrous ions and Dox, thereby achieving a trifunctional synergistic cancer therapy combining PTT, chemotherapy and ferroptosis for tumor ablation. RNA sequencing analysis of differentially expressed genes revealed that this therapy exerts multifaceted effects on cancer cell signaling. Cellular respiration and electron transport were significantly upregulated, while epigenetic pathways including chromatin modification and RNA transcriptional activity were severely downregulated, presenting an overall apoptotic effect. Thus, γ-Fe₂O₃-based nanostructures offer novel opportunities for efficient deep-tumor therapy. HeLa cells were treated with PBS, UF@PPDF NPs, and NIR-II 1064 nm laser irradiation (1.1 W cm⁻², 10 min). Subsequently, cells were continuously cultured for 2 hours prior to RNA sequencing. Data quality control was conducted, and raw data were preprocessed using Trimmomatics v0.38. The cleaned reads were aligned to the hg38 reference genome using HISAT v2.1.0. Fragment per kilobase of transcript per million mapped reads (FPKM) values were calculated using Rsubread and edgeR. Enrichment fold changes and p-values were quantified using edgeR and its negative binomial model.
提供机构:
秦燕
创建时间:
2023-01-15



