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Circ-IGF1R inhibits cell invasion and migration in non-small cell lung cancer.

ABSTRACT: BACKGROUND:Circular RNA (circRNA) is a novel molecular marker and target candidate that is closely associated with tumor invasion and migration. The mechanism of action of hsa_circ_0005035 (circ-IGF1R) in non-small cell lung cancer remains unclear. In this study, we aimed to study the mechanism of action of circ-IGF1R in lung cancer. METHODS:We screened circ-IGF1R, one of the most notable differential expressions, from the Gene Expression Omnibus database, GSE104854, for further research. The expression level of circ-IGF1R was examined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in five different lung cancer cell lines and 50 pairs of lung cancer and adjacent tissues. Wound-healing and Transwell assays were used for verifying the biological function of circ-IGF1R. The effect of overexpressing circ-IGF1R on the transcriptome of whole lung cancer cells was explored in lung cancer cell lines using RNA-seq. RESULTS:The expression level of circ-IGF1R was notably lower in lung cancer tissues and lung cancer cell lines than in the adjacent normal tissues and cells (P?

SUBMITTER: Xu Z

PROVIDER: S-EPMC7113055 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Circ-IGF1R inhibits cell invasion and migration in non-small cell lung cancer.

Xu Zhanyu Z Xiang Weiwei W Chen Wenjie W Sun Yu Y Qin Fanglu F Wei Jiangbo J Yuan Liqiang L Zheng Liping L Li Shikang S

Thoracic cancer 20200227 4

<h4>Background</h4>Circular RNA (circRNA) is a novel molecular marker and target candidate that is closely associated with tumor invasion and migration. The mechanism of action of hsa_circ_0005035 (circ-IGF1R) in non-small cell lung cancer remains unclear. In this study, we aimed to study the mechanism of action of circ-IGF1R in lung cancer.<h4>Methods</h4>We screened circ-IGF1R, one of the most notable differential expressions, from the Gene Expression Omnibus database, GSE104854, for further r ...[more]

PMID: 32107851

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Project description:BackgroundNumerous studies have shown that long non-coding RNAs (lncRNAs) play key roles during multiple cancer processes, such as cell proliferation, apoptosis, migration and invasion. The previous studies found that NKILA interacted with and suppressed the nuclear translocation of NF-KappaB, which influenced metastasis and prognosis in breast cancer. However the clinical significance and biological role of NKILA in non-small cell lung cancer (NSCLC) remains unknown.MethodsWe examined expression levels of NKILA in 106 pairs of NSCLC tissues and cell lines. The expression level of NKILA after TGF-?1 stimulation also was examined by qRT-PCR and validated by Chromatin immunoprecipitation (ChIP). Gain-of-function and loss-of-function assays were performed to examine the effect of NKILA on proliferation, migration and invasion of NSCLC cells. RNA immunoprecipitation (RIP), western blot and rescue experiments were carried out to reveal the interrelation between NKILA, NF-?B and EMT signal pathway.ResultsThe expression of NKILA was down-regulated in NSCLC cancer tissues compared with matched adjacent noncancerous tissues, and lower NKILA expression in tumor tissues were significantly correlated with lymph node metastasis and advanced TNM stage. We found that the expression of NKILA was mainly regulated by classical TGF-? signal pathway in NSCLC cells rather than NF-?B pathway reported in breast cancer. Gain and loss of function assays found that NKILA inhibited migration, invasion and viability of NSCLC cells. Mechanistic study showed that NKILA attenuated Snail expression via inhibiting the phosphorylation of I?B? and NF-?B activation, subsequently suppressed the expression of markers of epithelial-mesenchymal transition process.ConclusionsThe present study found that the expression of NKILA was downregulated in tumor tissues of NSCLC, which improved the metastasis of NSCLC patients. In vitro studies further clarified that the expression of NKILA was regulated through classical TGF-? signal pathway, which subsequently inhibited migration and invasion of NSCLC cells through interfering NF-?B/Snail signal pathway in NSCLC cells.

Dataset Information

Circ-IGF1R inhibits cell invasion and migration in non-small cell lung cancer.

Publications

Circ-IGF1R inhibits cell invasion and migration in non-small cell lung cancer.

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