DARS2通过ERK/c-Myc信号通路促进肺腺癌的发生。
DARS2 promotes the occurrence of lung adenocarcinoma via the ERK/c-Myc signaling pathway.
发表日期:2023 Nov 11
作者:
Tao Fang, Jin Jiang, Wenhao Yu, Rongyang Li, Hui Tian
来源:
Cellular & Molecular Immunology
摘要:
DARS2 表达在肺腺癌 (LUAD) 中上调,这与肿瘤患者分期和预后相关。 DARS2参与LUAD的机制仍需进一步探讨。在本研究中,我们发现DARS2在LUAD组织中的表达量显着高于正常组织。同时Kaplan-Meier曲线显示,DARS2高表达的LUAD患者生存预后明显差于DARS2低表达的患者。通过IHC染色、组织化学评分检测LUAD和邻近正常组织中DARS2的表达,并生成生存曲线。此外,我们证明DARS2的敲低和过表达显着影响体外和体内LUAD细胞的增殖、侵袭和迁移。最后对LUAD细胞进行蛋白质印迹和救援实验,进一步探索和验证信号通路。DARS2在LUAD组织和细胞系中表达显着上调。更重要的是,DARS2表达增加与增殖、侵袭和转移密切相关。裸鼠致瘤实验进一步表明,随着DARS2表达量的增加,裸鼠的致瘤能力明显增强。最后,我们确定 DARS2 通过靶向 ERK/c-Myc 信号通路在 LUAD 中发挥作用。我们的数据揭示了 DARS2 在 LUAD 中的致癌作用,表明 DARS2 可能是 LUAD 的预测生物标志物和新型治疗靶点。© 2023作者们。中国肺肿瘤学组与John Wiley联合出版《胸癌》
DARS2 expression is upregulated in lung adenocarcinoma (LUAD) which correlates with tumor patient stage and prognosis. The mechanism of DARS2 involvement in LUAD still needs to be further explored.In this study, we found that DARS2 expression in LUAD tissue was significantly higher than that in normal tissue. At the same time, the Kaplan-Meier curve showed that the survival prognosis of LUAD patients with high expression of DARS2 was significantly worse than low expression of DARS2. The expression of DARS2 was detected in LUAD and adjacent normal tissues by IHC staining, histochemical scoring and a survival curve was generated. In addition, we demonstrated that the knockdown and overexpression of DARS2 significantly affected the proliferation, invasion, and migration of LUAD cells in vitro and in vivo. Finally, western blot and rescue assay were performed on LUAD cells to further explore and verify the signaling pathway.DARS2 expression was significantly upregulated in LUAD tissues and cell lines. What is more, the increased expression of DARS2 was closely related to proliferation, invasion and metastasis. The tumorigenic assay in nude mice further showed that the tumorigenic ability of nude mice was significantly improved with the increase in DARS2 expression. Finally, we determined that DARS2 plays its role in LUAD by targeting the ERK/c-Myc signaling pathway.Our data revealed the oncogenic role of DARS2 in LUAD, indicating that DARS2 may be a predictive biomarker and novel therapeutic target for LUAD.© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.