The National Engineering Research Center for Bioengineering Drugs and the Technologies, the Institute of Translational Medicine, Nanchang University, Nanchang, China.
Department of Anesthesiology, the First Affiliated Hospital of Nanchang University, Nanchang, China.
J Cell Mol Med. 2021 Mar;25(6):3019-3030. doi: 10.1111/jcmm.16344. Epub 2021 Feb 4.
Aminoacyl-tRNA synthetase-interacting multifunctional protein-3 (AIMP3) is a tumour suppressor, however, the roles of AIMP3 in non-small cell lung cancer (NSCLC) are not explored yet. Here, we reported that AIMP3 significantly inhibited the cell growth and metastasis of NSCLC (lung adenocarcinoma) in vitro and in vivo. We have firstly identified that AIMP3 was down-regulated in human NSCLC tissues compared with adjacent normal lung tissues using immunohistochemistry and western blot assays. Overexpression of AIMP3 markedly suppressed the proliferation and migration of cancer cells in a p53-dependent manner. Furthermore, we observed that AIMP3 significantly suppressed tumour growth and metastasis of A549 cells in xenograft nude mice. Mechanically, we identified that AIMP3 was a direct target of miR-96-5p, and we also observed that there was a negative correlation between AIMP3 and miR-96-5p expression in paired NSCLC clinic samples. Ectopic miR-96-5p expression promoted the proliferation and migration of cancer cells in vitro and tumour growth and metastasis in vivo which partially depended on AIMP3. Taken together, our results demonstrated that the axis of miR-96-5p-AIMP3-p53 played an important role in lung adenocarcinoma, which may provide a new strategy for the diagnosis and treatment of NSCLC.
氨酰-tRNA 合成酶相互作用多功能蛋白-3(AIMP3)是一种肿瘤抑制因子,但 AIMP3 在非小细胞肺癌(NSCLC)中的作用尚未得到探索。在这里,我们报道了 AIMP3 显著抑制了 NSCLC(肺腺癌)的体外和体内细胞生长和转移。我们首次通过免疫组化和 Western blot 分析鉴定到 AIMP3 在人 NSCLC 组织中下调。AIMP3 的过表达以依赖 p53 的方式显著抑制癌细胞的增殖和迁移。此外,我们观察到 AIMP3 显著抑制了异种移植裸鼠中 A549 细胞的肿瘤生长和转移。在机制上,我们鉴定出 AIMP3 是 miR-96-5p 的直接靶标,并且我们还观察到在配对的 NSCLC 临床样本中 AIMP3 和 miR-96-5p 的表达呈负相关。外源性 miR-96-5p 表达促进了体外癌细胞的增殖和迁移以及体内肿瘤的生长和转移,这部分依赖于 AIMP3。总之,我们的研究结果表明,miR-96-5p-AIMP3-p53 轴在肺腺癌中发挥着重要作用,这可能为 NSCLC 的诊断和治疗提供新策略。