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

Chongyu Su; Yi Han; Hongtao Zhang; Yunsong Li; Ling Yi; Xiaojue Wang; Shijie Zhou; Daping Yu; Xiaoyun Song; Ning Xiao; Xiaoqing Cao; Zhidong Liu

doi:10.1111/jcmm.13587

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

J Cell Mol Med. 2018 Jun;22(6):3097-3107. doi: 10.1111/jcmm.13587. Epub 2018 Mar 13.

Authors

Chongyu Su¹, Yi Han¹, Hongtao Zhang², Yunsong Li¹, Ling Yi², Xiaojue Wang², Shijie Zhou¹, Daping Yu¹, Xiaoyun Song¹, Ning Xiao¹, Xiaoqing Cao¹, Zhidong Liu¹

Affiliations

¹ Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing, China.
² Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University and Beijing Tuberculosis and Thoracic Tumor Research Institute, 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.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

A549 Cells
Aged
Apoptosis / genetics
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / pathology
Cell Movement / genetics
Cell Proliferation / genetics
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
Humans
Kaplan-Meier Estimate
Male
MicroRNAs / genetics*
Middle Aged
NF-kappa B / genetics
Neoplasm Invasiveness / genetics
Neoplasm Invasiveness / pathology
RNA, Long Noncoding / genetics*
Signal Transduction / genetics
Transcription Factor RelA / genetics*

Substances

MIRN7 microRNA, human
MicroRNAs
NF-kappa B
RELA protein, human
RNA, Long Noncoding
Transcription Factor RelA
long non-coding RNA CDR1AS, human