AKT2 drives cancer progression and is negatively modulated by miR-124 in human lung adenocarcinoma.

Ting Liu, Jianjie Zhu, Wenwen Du, Weiwei Ning, Yang Zhang, Yuanyuan Zeng, Zeyi Liu, Jian-An Huang

Respiratory research 2020 Sep 01

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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). 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. 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. 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.

Citation

Ting Liu, Jianjie Zhu, Wenwen Du, Weiwei Ning, Yang Zhang, Yuanyuan Zeng, Zeyi Liu, Jian-An Huang. AKT2 drives cancer progression and is negatively modulated by miR-124 in human lung adenocarcinoma. Respiratory research. 2020 Sep 01;21(1):227