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

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.

Anticancer potential of turmeric (Curcuma longa) ethanol extract and prediction of its mechanism through the Akt1 pathway

“…74 Previous studies mentioned that Akt2 silencing in A549 and H1299 cell lines did not affect their apoptosis. 75 Meanwhile, not much is known about the role of Akt3 in breast cancer. 50 Although AZD5363 targeted for Akt family (Akt1, Akt2, and Akt3), 76 AZD5363 is a positive control in this molecular docking to assess the binding affinity and binding site of turmeric compounds interacting with Akt1.…”

Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance

“…A mutated form of the PIK3CA protein was also found to selectively phosphorylate AKT and FOXO promoting cellular growth and cancer cell invasion [119]. The AKT2 gene is often amplified in human cancers, including lung and ovarian cancers while both AKT1 and AKT2 gene amplification has been reported in breast and colorectal cancers [120][121][122][123][124]. As previously mentioned, PTEN is responsible for the indirect inactivation of AKT by converting PIP3 to PIP2, thus acting as a tumor suppressor.…”

Tumor Suppressive Effects of miR-124 and Its Function in Neuronal Development

“…In the pathogenesis of lung cancer, Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation-driven lung cancer causes increased aggressiveness and tumor size by gene ablation of the miRNA processing enzyme DICER1 [53], suggesting that miRNA functions are important for suppressing cancer. In non-small cell lung cancer (NSCLC), miR-124 suppresses cell proliferation, inhibits invasion and metastasis, and induces apoptosis [32,[54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] (Table 2).…”