Long non-coding RNA NKILA inhibits migration and invasion of non-small cell lung cancer via NF-κB/Snail pathway

Abstract

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-β1 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-κB 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-β signal pathway in NSCLC cells rather than NF-κB 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 IκBα and NF-κB 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-β signal pathway, which subsequently inhibited migration and invasion of NSCLC cells through interfering NF-κB/Snail signal pathway in NSCLC cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0518-0) contains supplementary material, which is available to authorized users.

LncRNA NKILA correlates with the malignant status and serves as a tumor‐suppressive role in rectal cancer

“…In nonsmall cell lung cancer, Lu et al 14 reported NKILA low-expression in cancer tissue samples was associated with lymph node metastasis and advanced TNM stage. In nonsmall cell lung cancer, Lu et al 14 reported NKILA low-expression in cancer tissue samples was associated with lymph node metastasis and advanced TNM stage.…”

“…15,16 Moreover, Yang et al 18 demonstrated that knockdown of NKILA expression promoted cell viability and migration, and reversed cell apoptosis F I G U R E 4 The molecular mechanism of NKILA in rectal cancer cell. [14][15][16][17][18][19][20] In addition, NKILA was found to enhance the the anticancer effects of baicalein in hepatocellular carcinoma through modulating NF-κB signaling. B, NKILA overexpression inhibits p65 nuclear translocation and induces p65 cytoplasmic retention and the cytotoxicity of X-ray radiation.…”

MEG3 Suppresses Human Pancreatic Neuroendocrine Tumor Cells Growth and Metastasis by Down-Regulation of Mir-183

“…Since their discoveries, a large amount of lncRNA has been found being dysregulated in a range of cancers [5]. In addition, they are being identified and characterized for serial steps of cancer development, including tumor initiation, growth, and metastasis [6].…”

Long non‐coding RNAs: How to regulate the metastasis of non–small‐cell lung cancer

“…NF‐κB interacting LncRNA (NKILA), encoded by a gene at chromosome 20q13 just near by the prostate transmembrane protein androgen induced 1 (PMEPA1), was increased by NF‐κB in breast cancer . Recently, Lu et al discovered that NKILA expression was negatively associated with tumour metastasis in patients with NSCLC, and the expression of NKILA was regulated through classical TGF‐β signal pathway, which subsequently inhibited migration and invasion of NSCLC cells through interfering NF‐κB/Snail signal pathway in NSCLC cells …”