Diminished LINC00173 expression induced miR-182-5p accumulation promotes cell proliferation, migration and apoptosis inhibition via AGER/NF-κB pathway in non-small-cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors in the world, and non-coding RNA (ncRNA) has recently been widely reported to participate in the development of NSCLC. Some ncRNAs, especially microRNAs (miRNAs), are widely reported as tumor drug targets due to their short transcript length and easiness for processing into small molecule compounds. Therefore, exploring the potential roles of specific miRNAs in NSCLC may provide a better understanding of the molecular etiology. In this study, we downloaded the large-scale RNA-seq data from the Cancer Genome Atlas (TCGA) database, and identified 211 differentially expressed miRNAs (121 up-regulated and 90 down-regulated) in NSCLC. Similar to the TCGA database, miR-182-5p was significantly up-regulated in the serum and tissue samples of NSCLC patients. Clinicopathological parameters revealed the positive correlation between miR-182-5p expression and advanced TNM stage. Functional tests showed miR-182-5p overexpression promoted cell proliferation, migration and apoptosis inhibition, while miR-182-5p knockdown weakened the above phenotypes. Besides, advanced glycosylation end-product specific receptor (AGER) was identified as a direct downstream target of miR-182-5p. Alteration of AGER expression or NF-κB inhibitor could partially counteract the bioactive roles induced by miR-182-5p overexpression or knockdown. Further study disclosed down-regulated LINC00173 was negatively corrected with miR-182-5p in NSCLC tissues. LINC00173 could regulate miR-182-5p expression and reversed functional behaviors mediated by miR-182-5p/AGER/NF-κB axis. Taken together, miR-182-5p mediated the malignant phenotypes through NF-κB pathway via targeting AGER, and LINC00173 acted as a potential negative regulator of miR-182-5p in NSCLC cells.