Targeting the HMGA2 oncogene by miR-498 inhibits non-small cell lung cancer biological behaviors

N. Gao, F.-X. Wang, G. Wang, Q.-S. Zhao

The Intensive Care Unit (ICU), Jining No. 1 People’s Hospital, Jining, Shandong, China. zq397614@126.com

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• Oncology

OBJECTIVE: Previous study reported that miR-498 served as a tumor suppressor in non-small cell lung cancer (NSCLC), but the underlying mechanism remains largely unknown. The aim of this study is to investigate the role of miR-498 and its target gene HMGA2 in NSCLC progression.

PATIENTS AND METHODS: The expression of miR-498 was assessed in clinical NSCLC specimens and cell lines using RT-PCR. Overexpression of miR-498 and transfection of pLenti-HMGA2 were performed in A549 cells. Cell proliferation, apoptosis, migration, and invasion were determined using cell counting kit-8 (CCK-8) assay, clone formation assay, flow cytometry, and transwell assay, respectively. Luciferase reporter assays were performed to analyze the regulation of putative target of miR-498. Western blot was used to detect the levels of HMGA2 in A549 cells.

RESULTS: MiR-498 was found to be down-regulated in NSCLC tissues and cell lines. After miR-498 mimics transfection, cell proliferation, migration, and invasion were significantly suppressed in the NSCLC cells. Mechanistically, bioinformatic analysis predicted that miR-498 may target the 3’-UTR of HMGA2 and suppressed its translation, and was further confirmed by luciferase assay. Furthermore, restoration of HMGA2 expression completely rescued the inhibitory effect of miR-498 in NSCLC cells.

CONCLUSIONS: This paper revealed that miR-498 may serve as a tumor suppressor in NSCLC through targeting HMGA2, suggesting that miR-498 could represent a novel target for effective therapies.

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