AKT2 drives cancer progression and is negatively modulated by miR-124 in human lung adenocarcinoma
AKT2 drives cancer progression and is negatively modulated by miR-124 in human lung adenocarcinoma
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在人肺腺癌中，AKT2 驱动癌症进展并受到 miR-124 的负向调节
DOI：
10.1186/s12931-020-01491-0
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发表时间：
2020-09-01
影响因子：
5.8
通讯作者：
Huang, Jian-An
中科院分区：
文献类型：
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作者：
Liu, Ting;Zhu, Jianjie;Huang, Jian-An
背景：AKT2在包括非小细胞肺癌(NSCLC)在内的许多人类肿瘤中高度表达。越来越多的证据也表明，AKT2可以促进NSCLC细胞的增殖和转移。然而，其中涉及的机制仍不清楚。因此，本研究主要探讨AKT2在肺腺癌(LUAD)发生发展中的作用，揭示AKT2在肺腺癌(LUAD)中转录后表达的新机制。方法采用实时定量(qRT-PCR)、免疫印迹和免疫组织化学(IHC)方法检测AKT2等蛋白在肺腺癌中的表达。细胞计数试剂盒-8(CCK-8)、集落形成和EDU实验检测细胞增殖情况。用流式细胞仪检测细胞周期和细胞凋亡的变化。Transwell法检测细胞迁移和侵袭能力。此外，荧光素酶报告实验和Western blotting被用来评估miR-124靶向AKT2。采用小鼠移植瘤模型，观察miR-124/AKT2轴在LUAD发生发展中的作用。结果AKT2在非小细胞肺癌组织中高表达，并与LUAD患者预后不良密切相关。此外，AKT2通过调节细胞周期、促进上皮-间充质转化(EMT)的发生和基质金属蛋白酶(MMPs)的表达而影响LUAD细胞的增殖、迁移和侵袭。此外，我们还发现miR-124过表达通过与AKT2的3‘-非翻译区结合而下调AKT2的表达，从而抑制了LUAD的发生和发展。结论miR-124过表达可以负向调节AKT2，从而抑制LUAD的进展。因此，miR-124/AKT2轴可能成为LUAD新疗法的潜在靶点。
BackgroundAKT2 is highly expressed in many human cancers, including non-small cell lung cancer (NSCLC). Accumulating evidence has also revealed that AKT2 can promote NSCLC cell proliferation and metastasis. However, the involved mechanism remains unclear. Herein, our study mainly explored the function of AKT2 during cancer progression and uncovered a new post-transcriptional mechanism of AKT2 expression in lung adenocarcinoma (LUAD).MethodsQuantitative real-time (qRT-PCR), western blot and immunohistochemistry (IHC) assays were performed to detect the expression of AKT2 and other proteins. Cell counting kit-8 (CCK-8), colony formation and EdU assays were performed to assess cell proliferation. Flow cytometry analysis was used to detect changes in the cell cycle and apoptosis. Transwell assays were used to evaluate cell migration and invasion. Additionally, a luciferase reporter assay and western blotting were employed to assess miR-124 targeting of AKT2. Xenograft mouse model was used to observe the role of miR-124/AKT2 axis on the occurrence and development of LUAD.ResultsWe showed that AKT2 was highly expressed in NSCLC tissues and closely related to the poor prognosis of LUAD patients. Moreover, AKT2 affected LUAD cell proliferation, migration and invasion by regulating the cell cycle and promoting the occurrence of epithelial-mesenchymal transition (EMT) and the expression of matrix metalloproteinases (MMPs). In addition, we demonstrated that miR-124 overexpression downregulated AKT2 expression by binding to the 3′-untranslated region (3′- UTR) of AKT2 and thus inhibited the occurrence and development of LUAD in vivo and in vitro.ConclusionsOur results suggest that miR-124 overexpression can negatively regulate AKT2 and thus inhibit the progression of LUAD. Therefore, the miR-124/AKT2 axis may serve as a potential target for novel therapies for LUAD.