MiR-449a suppresses tumor growth, migration and invasion in non-small cell lung cancer by targeting HMGB1-mediated NF-κB signaling way

Dandan Wu, Jun Liu, Jianliang Chen, Haiyan He, Hang Ma, Xuedong Lv
Oncology Research 2018 March 21
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 associated with tumor growth, migration and invasion. However, its expression and function in non-small cell lung cancer (NSCLC) still remain unclear. In our study, miR-449a was found to be down-regulated both in 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 up-regulation of HMGB1 could reverse the miR-449a-induced suppression of growth, migration and invasion in NSCLC cells. Lastly, we found that miR-449a suppressed tumor initiation and development through NF-κB signaling way. These results indicate that miR-449a functions as a tumor suppressor in NSCLC by targeting HMGB1-mediated NF-κB signaling way in NSCLC.

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