cLMNB1的m6A修饰通过去稳定FGFR4克服非小细胞肺癌奥希替尼耐药

数据集获取

源站：https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272182

标准获取流程：

1. 访问源站链接，注册/登录账号；
2. 进入数据集详情页，按页面指引申请权限或直接下载；
3. 部分平台提供 SDK，例如：
   • OpenDataLab: pip install openxlab 后 openxlab.dataset.get(...)
   • ModelScope: pip install modelscope 后 modelscope download
   • 天池: 登录后页面提供直链下载
     以源站「数据下载/使用文档」页面为准。

数据说明

Background: Osimertinib resistance is the main challenge of the treatment in EGFR mutant lung adenocarcinoma (LUAD). The role of N6-methyladenosine (m6A) modification of circular RNAs (circRNAs) in osimertinib-resistant LUAD remains largely unknown. Methods: Parental and resistant cell lines, as well as human and mouse lung tissue samples were implemented. We used MeRIP-seq and circRNA-seq to screen the potential circRNA candidate that influenced osimertinib resistance. The sensitivity of LUAD cells was detected by Cell Counting Kit-8 (CCK-8) assay. The interaction between circRNA and proteins was validated by RNA immunoprecipitation and RNA pulldown. We generated circRNA encapsulated in lipid nanoparticle (LNP). Bioluminescence imaging assay was used for the monitoring of orthotopic transplantation model. Results: It was observed that circRNA LMNB1 (cLMNB1) exhibited elevated levels of m6A modification and diminished expression in osimertinib-resistant LUAD. cLMNB1 increased the sensitivity of LUAD to osimertinib in vitro and in vivo. METTL3 increased the m6A modification of cLMNB1 and inhibited its expression through the reading protein YTHDF2. cLMNB1 acted as a scaffold between Fibroblast growth factor receptor 4 (FGFR4) and E3 ubiquitin-protein ligase CBL (c-Cbl), enhancing the ubiquitin-dependent degradation of FGFR4. cLMNB1 with mutation of m6A modification site (cLMNB1-mut) encapsulated in LNP increased the efficacy of osimertinib in resistant LUAD. Conclusions: Our findings demonstrated that METTL3 and YTHDF2 mediated cLMNB1 degradation in m6A-dependent manner, and cLMNB1 destabilized FGFR4 protein in a ubiquitin-dependent way. We propose cLMNB1-mut as a nucleic acid drug that can overcome osimertinib resistance for its efficacy in osimertinib-resistant pre-clinical models in LUAD.

数据加载示例（图像类）

from PIL import Image
import glob, os

files = (glob.glob(os.path.join(path, "**", "*.png"), recursive=True)
       + glob.glob(os.path.join(path, "**", "*.jpg"), recursive=True)
       + glob.glob(os.path.join(path, "**", "*.tif"), recursive=True))
print("图像文件数:", len(files))
img = Image.open(files[0]); print("尺寸/模式:", img.size, img.mode)

# torchvision Dataset 方式:
# from torchvision import datasets
# ds = datasets.ImageFolder(path)  # 要求 子目录=类别

目录组织与标注格式以源站说明和下载后实际文件为准。