AIMP3 inhibits cell growth and metastasis of lung adenocarcinoma through activating a miR-96-5p-AIMP3-p53 axis.
AIMP3 inhibits cell growth and metastasis of lung adenocarcinoma through activating a miR-96-5p-AIMP3-p53 axis.
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AIMP3 通过激活 miR-96-5p-AIMP3-p53 轴抑制肺腺癌的细胞生长和转移。
DOI：
10.1111/jcmm.16344
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发表时间：
2021-03
影响因子：
5.3
通讯作者：
Xin H
中科院分区：
文献类型：
--
作者：
Ding L;Fang Y;Li Y;Hu Q;Ai M;Deng K;Huang X;Xin H
氨酰-tRNA合成酶相互作用多功能蛋白-3（AIMP 3）是一种肿瘤抑制因子，然而，AIMP 3在非小细胞肺癌（NSCLC）中的作用尚未探索。本文报道了AIMP 3在体外和体内均能显著抑制NSCLC细胞的生长和转移。我们首先使用免疫组织化学和蛋白质印迹分析确定，与邻近的正常肺组织相比，AIMP 3在人NSCLC组织中下调。AIMP 3的过表达以p53依赖的方式显著抑制癌细胞的增殖和迁移。此外，我们观察到AIMP 3显著抑制异种移植裸鼠中A549细胞的肿瘤生长和转移。从机制上讲，我们确定了AIMP 3是miR-96 - 5 p的直接靶点，我们还观察到配对NSCLC临床样本中AIMP 3和miR-96 - 5 p表达之间存在负相关性。异位miR-96 - 5 p表达在体外促进癌细胞的增殖和迁移，在体内促进肿瘤的生长和转移，这部分依赖于AIMP 3。综上所述，我们的研究结果表明miR-96 - 5 p-AIMP 3-p53轴在肺腺癌中发挥重要作用，这可能为NSCLC的诊断和治疗提供新的策略。
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.
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