CiRS-7 targeting miR-7 modulates the progression of non-small cell lung cancer in a manner dependent on NF-κB signalling

Abstract

The purpose of this study was to figure out the effect of ciRS-7/miR-7/NF-κB axis on the development of non-small cell lung cancer (NSCLC). In response, the expressions of ciRS-7, miR-7 and NF-κB subunit (ie RELA) within NSCLC tissues and cell lines were determined with real-time polymerase chain reaction (RT-PCR) and Western blot. Moreover, the NSCLC cells were transfected with pcDNA3-ciRS-7-ir, pcDNA3-ciRS-7, miR-NC and miR-7 mimic. Furthermore, the targeted relationships between ciRS-7 and miR-7, as well as between miR-7 and RELA, were confirmed by luciferase reporter assay. The proliferation, migration and apoptosis of NSCLC cells were, successively, measured using CCK-8 assay, wound-healing assay and flow cytometry test. Consequently, ciRS-7, miR-7, histopathological grade, lymph node metastasis and histopathological stage could independently predict the prognosis of patients with NSCLC (all P < .05). Moreover, remarkably up-regulated ciRS-7 and RELA expressions, as along with down-regulated miR-7 expressions, were found within NSCLC tissues and cells in comparison with normal ones (P < .05). Besides, overexpressed ciRS-7 and underexpressed miR-7 were correlated with increased proliferation, migration and invasion, yet reduced apoptosis rate of NSCLC cells (P < .05). More than that, ciRS-7 specifically targeted miR-7 to reduce its expressions (P < .05). Ultimately, the NSCLC cells within miR-7 + RELA group were observed with superior proliferative, migratory and invasive capabilities than those within miR-7 group (P < .05), and RELA expression was also significantly modified by both ciRS-7 and miR-7 (P < .05). In conclusion, the ciRS-7/miR-7/NF-kB axis could exert pronounced impacts on the proliferation, migration, invasion and apoptosis of NSCLC cells.

Keywords: CiRS-7; NF-kB; cell activity; cell apoptosis; cell invasion; cell migration; miR-7; non-small cell lung cancer.