Open Access

ARTICLE

miR-449a Suppresses Tumor Growth, Migration, and Invasion in Non-Small Cell Lung Cancer by Targeting a HMGB1-Mediated NF-kB Signaling Pathway

Dandan Wu^*1, Jun Liu^†1, Jianliang Chen^*, Haiyan He^*, Hang Ma^*, Xuedong Lv^*

* Department of Respiratory Medicine, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, P.R. China
† Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, P.R. China

Oncology Research 2019, 27(2), 227-235. https://doi.org/10.3727/096504018X15213089759999

Abstract

MicroRNAs (miRNAs) have been reported to be involved in many human cancers and tumor progression. The dysregulation of miR-449a is found in many types of malignancies and is associated with tumor growth, migration, and invasion. However, its expression and function in non-small cell lung cancer (NSCLC) still remains unclear. In our study, miR-449a was found to be downregulated in both NSCLC tissues and cell lines, and low miR-449a expression was obviously associated with tumor differentiation, TMN stage, and poor overall survival (OS). Moreover, we demonstrated that miR-449a could inhibit tumor proliferation, migration, and invasion in NSCLC. We also confirmed that HMGB1 was a direct target gene of miR-449a in NSCLC with dual-luciferase reporter assay, and upregulation of HMGB1 could reverse the miR-449a-induced suppression of growth, migration, and invasion in NSCLC cells. Last, we found that miR-449a suppressed tumor initiation and development through the NF- B signaling pathway. These results indicate that miR-449a functions as a tumor suppressor in NSCLC by targeting the HMGB1-mediated NF- B signaling pathway in NSCLC.

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