MAGI1-IT1 stimulates proliferation in non-small cell lung cancer by upregulating AKT1 as a ceRNA

G. Zhang, H.-X. Chen, S.-N. Yang, J. Zhao

Department of Oncology, Mudanjiang Cancer Hospital, Mudanjiang, China. ohjerry@163.com

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• Oncology

OBJECTIVE: This study aims to illustrate the potential role of MAGI1-IT1 in the progression of non-small cell lung cancer (NSCLC) and the underlying mechanism.
PATIENTS AND METHODS: The relative level of MAGI1-IT1 in normal lung tissues and NSCLC tissues was determined. Its level in NSCLC patients with different tumor sizes (<5 cm or >5 cm), metastatic statues (positive or negative), and tumor staging (stage I+II or stage III+IV) was detected as well. The prognostic potential of MAGI1-IT1 in evaluating the overall survival (OS) and progression-free survival (PFS) of NSCLC patients was assessed by the Kaplan-Meier method. In A549 and PC-9 cells, the regulatory effect of MAGI1-IT1 on the proliferative ability was examined by the cell counting kit-8 (CCK-8), colony formation, and 5-Ethynyl-2’-deoxyuridine (EdU) assay. The target miRNA of MAGI1-IT1 and the target gene binding to miRNA-512-3p were predicted using the Diana database. The interactions among MAGI1-IT1/miRNA-512-3p/AKT1 regulatory loop were tested by the Dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. At last, the rescue experiments were carried out to uncover the regulatory effect of MAGI1-IT1/AKT1 axis on NSCLC progression.
RESULTS: MAGI1-IT1 was upregulated in NSCLC tissues. Its level was higher in NSCLC patients with larger tumor size, positive metastasis, or advanced stage. High level of MAGI1-IT1 predicted worse OS and PFS in NSCLC patients. The knockdown of MAGI1-IT1 remarkably attenuated the proliferative ability in A549 and PC-9 cells. MAGI1-IT1 could target miRNA-512-3p, and AKT1 was the target gene of miR-512-3p. The overexpression of AKT1 stimulated lung cancer cells to proliferate. Of note, the elevated proliferative rate in lung cancer cells overexpressing AKT1 was reversed by the silence of MAGI1-IT1.
CONCLUSIONS: MAGI1-IT1 is upregulated in NSCLC tissues and cell lines, and predicts a poor prognosis in NSCLC patients. MAGI1-IT1 stimulates proliferative ability in NSCLC by upregulating the AKT1 level by binding to miRNA-512-3p.

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