AKT2 drives cancer progression and is negatively modulated by miR-124 in human lung adenocarcinoma
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RESEARCH
Open Access
AKT2 drives cancer progression and is negatively modulated by miR-124 in human lung adenocarcinoma Ting Liu1,2†, Jianjie Zhu1,2†, Wenwen Du1,2, Weiwei Ning1, Yang Zhang1,2, Yuanyuan Zeng1,2,3* , Zeyi Liu1,2* and Jian-An Huang1,2,4*
Abstract Background: AKT2 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). Methods: Quantitative 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. Results: We 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. Conclusions: Our 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. Keywords: Lung adenocarcinoma, AKT2, Proliferation, Migration, Invasion, miR-124
* Correspondence: [email protected]; [email protected]; [email protected] † Ting Liu and Jianjie Zhu contributed equally to this work. 1 Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou 215006, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence,
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