miR-449a Suppresses Tumor Growth,Migration, and Invasion in Non-Small Cell Lung Cancer by Targeting a HMGB1-Mediated NF-kB Signaling Pathway |
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Authors: | Dandan Wu Jun Liu Jianliang Chen Haiyan He Hang Ma Xuedong Lv |
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Institution: | * 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 |
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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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Keywords: | miR-449a Non-small cell lung cancer (NSCLC) High-mobility group box 1 (HMGB1) NF- B |
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