Zeng Zihang, Zhang Jianguo, Li Jiali, Li Yangyi, Huang Zhengrong, Han Linzhi, Xie Conghua, Gong Yan
Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
Front Genet. 2022 Aug 10;13:935601. doi: 10.3389/fgene.2022.935601. eCollection 2022.
Lung adenocarcinoma (LUAD) has high morbidity and mortality worldwide, and its prognosis remains unsatisfactory. Identification of epigenetic biomarkers associated with radiosensitivity is beneficial for precision medicine in LUAD patients. SETD2 is important in repairing DNA double-strand breaks and maintaining chromatin integrity. Our studies established a comprehensive analysis pipeline, which identified SETD2 as a radiosensitivity signature. Multi-omics analysis revealed enhanced chromatin accessibility and gene transcription by SETD2. In both LUAD bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq), we found that SETD2-associated positive transcription patterns were associated with DNA damage responses. SETD2 knockdown significantly upregulated tumor cell apoptosis, attenuated proliferation and migration of LUAD tumor cells, and enhanced radiosensitivity . Moreover, SETD2 was a favorably prognostic factor whose effects were antagonized by the m6A-related genes RBM15 and YTHDF3 in LUAD. In brief, SETD2 was a promising epigenetic biomarker in LUAD patients.
肺腺癌（LUAD）在全球范围内具有较高的发病率和死亡率，其预后仍然不尽人意。鉴定与放射敏感性相关的表观遗传生物标志物有助于LUAD患者的精准医疗。SETD2在修复DNA双链断裂和维持染色质完整性方面很重要。我们的研究建立了一个综合分析流程，该流程将SETD2鉴定为一种放射敏感性特征。多组学分析揭示了SETD2增强的染色质可及性和基因转录。在LUAD批量RNA测序（RNA-seq）和单细胞RNA测序（scRNA-seq）中，我们发现与SETD2相关的阳性转录模式与DNA损伤反应有关。SETD2敲低显著上调肿瘤细胞凋亡，减弱LUAD肿瘤细胞的增殖和迁移，并增强放射敏感性。此外，SETD2是一个有利的预后因素，其作用在LUAD中被m6A相关基因RBM15和YTHDF3拮抗。简而言之，SETD2是LUAD患者中一个有前景的表观遗传生物标志物。
