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CiRS-7 targeting miR-7 modulates the progression of non-small cell lung cancer in a manner dependent on NF-κB
Chongyu Su1, Yi Han1, Hongtao Zhang2
1Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing, China.
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.
Insights
The ciRS-7/miR-7/NF-κB axis significantly impacts non-small cell lung cancer (NSCLC) development. Upregulated ciRS-7 and NF-κB, with downregulated miR-7, promote NSCLC proliferation and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide.
- Understanding the molecular mechanisms driving NSCLC progression is crucial for developing effective therapeutic strategies.
- The role of circular RNAs (circRNAs) and their interactions with microRNAs (miRNAs) in cancer is an emerging area of research.
Purpose of the Study:
- To investigate the functional role of the ciRS-7/miR-7/NF-κB signaling axis in the pathogenesis of non-small cell lung cancer.
- To elucidate the molecular interactions between ciRS-7, miR-7, and the NF-κB pathway component RELA in NSCLC cells.
Main Methods:
- Quantitative real-time polymerase chain reaction (RT-PCR) and Western blot analysis to assess gene and protein expression levels.
- Luciferase reporter assays to confirm direct targeting interactions between ciRS-7, miR-7, and RELA.
- In vitro functional assays including CCK-8, wound-healing, and flow cytometry to evaluate cell proliferation, migration, invasion, and apoptosis.
Main Results:
- ciRS-7 and RELA were significantly upregulated, while miR-7 was downregulated in NSCLC tissues and cell lines compared to normal controls.
- Overexpression of ciRS-7 and underexpression of miR-7 correlated with increased NSCLC cell proliferation, migration, and invasion, and decreased apoptosis.
- ciRS-7 directly targets and downregulates miR-7, and the ciRS-7/miR-7/NF-κB axis significantly influences NSCLC cell behavior.
Conclusions:
- The ciRS-7/miR-7/NF-κB axis plays a critical role in promoting the proliferation, migration, and invasion of non-small cell lung cancer cells.
- Aberrant expression of ciRS-7, miR-7, and RELA are potential prognostic biomarkers for NSCLC.
- Targeting the ciRS-7/miR-7/NF-κB pathway may represent a novel therapeutic strategy for NSCLC treatment.
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