Identifying circRNA-miRNA-mRNA Networks Associated with Osimertinib Resistance in Lung Adenocarcinoma by Analyzing Microarray Datasets.

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Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer Pub Date : 2025-01-01 DOI:10.1615/JEnvironPatholToxicolOncol.2024054531

Fen Liu, Xiyan Wang, Wenjun Tian, Xueli Dong, Guanghai Wang

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Abstract

Background: This study was to screen for circRNAs associated with osimertinib resistance in lung adenocarcinoma (LUAD) and establish a circRNA-miRNA-mRNA ceRNA network.

Methods: DESeq2 analysis was used to identify circRNAs in GEO database associated with osimertinib resistance in LUAD. Differentially expressed miRNAs in LUAD intersected with the target miRNAs of circRNA. Predicted target gene for miRNAs were overlapped with the co-expressed genes of EGFR. Hsa_circ_0078465/miR-183-5p/NRAS axis was validated in cells.

Results: Osimertinib resistance-related circRNAs in LUAD were linked to six differentially expressed miRNAs and 35 EGFR-related mRNAs. NRAS was the hub gene. These mRNAs were associated with cell motility regulation, non-small cell lung cancer and EGFR tyrosine kinase inhibitor resistance pathway. The cell proliferation and migration assays confirmed the promoting role of hsa_circ_0078465/miR-183-5p/NRAS axis in osimertinib-resistant cells.

Conclusion: A circRNA-miRNA-mRNA network associated with osimertinib resistance in LUAD proposed hsa_ circ_0078465/miR-183-5p/NRAS axis.

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通过分析微阵列数据集鉴定肺腺癌中与奥西替尼耐药相关的circRNA-miRNA-mRNA网络

背景：本研究旨在筛选肺腺癌（LUAD）中与奥西替尼耐药相关的circrna，并建立circRNA-miRNA-mRNA ceRNA网络。方法：采用DESeq2分析方法鉴定GEO数据库中与LUAD患者奥西替尼耐药相关的circrna。LUAD中差异表达的mirna与circRNA的靶mirna相交。预测的mirna靶基因与EGFR共表达基因重叠。Hsa_circ_0078465/miR-183-5p/NRAS轴在细胞中得到验证。结果：LUAD中与奥西替尼耐药相关的环状rna与6个差异表达的mirna和35个egfr相关的mrna相关。NRAS是中心基因。这些mrna与细胞运动调节、非小细胞肺癌和EGFR酪氨酸激酶抑制剂耐药途径相关。细胞增殖和迁移实验证实了hsa_circ_0078465/miR-183-5p/NRAS轴在奥西替尼耐药细胞中的促进作用。结论：与LUAD中奥西替尼耐药相关的circRNA-miRNA-mRNA网络提出了hsa_ circ_0078465/miR-183-5p/NRAS轴。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer

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