MiRNA-488-3p inhibits malignant progression of NSCLC by modulating ADAM9

Y. Wu, Y. Wu, X.-Y. Chen, Y.-X. Niu, F.-Z. Lv, W. Gao

Department of Thoracic Surgery, Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Shanghai, China. fanzhenlv@163.com

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• Oncology

OBJECTIVE: The purpose of this study was to investigate the role of microRNA-488-3p in the proliferation, invasion and migration of lung cancer cells and to further explore the potential regulatory mechanisms.

PATIENTS AND METHODS: MicroRNA-488-3p expression in 46 pairs of tumor tissue and paracancerous tissue specimens collected from non-small cell lung cancer (NSCLC) patients were measured through quantitative real-time polymerase chain reaction (qRT-PCR) method, and the interplay between microRNA-488-3p expression and some clinical indicators of these subjects was also analyzed. In addition, microRNA-488-3p overexpression models were constructed in NSCLC cell lines, and then Cell Counting Kit-8 (CCK-8) test and transwell assays were carried out to evaluate the effect of microRNA-488-3p on the NSCLC cell functions. Furthermore, bioinformatics analysis and luciferase reporter gene assay were carried out to uncover the potential interaction between microRNA-488-3p and its downstream gene ADAM9.

RESULTS: QPCR results revealed that microRNA-488-3p showed a significant lower expression in NSCLC tissue samples than in adjacent normal ones. In comparison to patients with high expression of microRNA-488-3, patients with low expression of microRNA-488-3 exhibited higher incidence of lymph node or distant metastasis and lower survival rate. In vitro cell experiments showed that, in comparison to control group, overexpression of microRNA-488-3p significantly weakened the proliferation ability as well as the invasion and migration of NSCLC cells. Subsequently, a significant increase in ADAM9 expression in NSCLC tissue samples was found, which indicated its negative correlation with microRNA-488-3p. In addition, cell recovery experiment demonstrated that overexpression of ADAM9 could counteract the impact of microRNA-488-3p upregulation on the proliferation and invasion ability of NSCLC cells, and the two may thus together affect the malignant progression of NSCLC.

CONCLUSIONS: It can be concluded that microRNA-488-3p, which is associated with the incidence of metastasis in NSCLC patients, can inhibit the malignant progression of NSCLC cells by modulating ADAM9 expression.

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