NKILA inhibits NF-κB signaling and suppresses tumor metastasis

Abstract

The long non-coding RNA (lncRNA) NKILA (nuclear transcription factor NF-κB interacting lncRNA) functions as a suppressor in human breast cancer and tongue cancer. However, the clinical significance and biological roles of NKILA in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we showed that NKILA was downregulated in ESCC tissues and cancer cells compared with their normal counterparts. Low NKILA expression correlated with large tumor size and advanced TNM stage, and predicted poor overall and disease-free survival of ESCC patients. Further loss- and gain-of-function assays indicated that NKILA inhibited proliferation and migration of ESCC cells in vitro, suppressed tumor growth and lung metastasis in vivo. Mechanistically, NKILA could inhibit phosphorylation of IκBα, suppress p65 nuclear translocation and downregulate the expression of NF-κB target genes in ESCC cells. These results suggest NKILA could suppress malignant development of ESCC via abrogation of the NF-κB signaling and may potentially serve as a prognostic marker for ESCC.

LncRNA NKILA suppresses TGF‐β‐induced epithelial–mesenchymal transition by blocking NF‐κB signaling in breast cancer

“…Our data showed that inference of NKILA did not significantly alter either TAK1 phosphorylation or miR‐182 levels. In addition, it has been reported that NKILA promotes the metastasis of esophageal squamous cell carcinoma via MMP9 and MMP14 . Consistent with our data, MMP9 and MMP14 are regulated by NF‐κB and play a significant role in EMT .…”

“…In addition, it has been reported that NKILA promotes the metastasis of esophageal squamous cell carcinoma via MMP9 48 and MMP14. 49 Consistent with our data, MMP9 and MMP14 are regulated by NF-jB [50][51][52] and play a significant role in EMT. 53 Together, these data indicate that NKILA mediates TGF-binduced EMT by negatively regulating several NF-jB target genes.…”

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

“…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. We found NKILA overexpression dramatically repressed rectal cancer cell proliferation, migration, and invasion.…”

“…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.…”

LncRNA HOXA‐AS2 positively regulates osteogenesis of mesenchymal stem cells through inactivating NF‐κB signalling

“…Long non‐coding RNAs, a subset of non‐coding transcripts with more than 200 nucleotides in length, have been shown to play important roles in numerous biological processes, for example inflammation, immunity and various cancers . With the development of high throughput RNA sequencing approach, a variety of novel lncRNAs were identified.…”