Gastric Cancer

BANCR[LncRNA]

miR-532-5p[miRNA]

NCF2[mRNA]

MNK-45, SGC-7901, HGC-27, BGC-23, and AGS

Homo sapiens (human)

Oncogene 2018 May 37, 2660-2675 doi:10.1038/s41388-018-0162-y PMID:29483646

LINC01410-miR-532-NCF2-NF-kB feedback loop promotes gastric cancer angiogenesis and metastasis.

RNA-seq,Microarray,RT-qPCR,Western blot,Luciferase reporter assay,in vitro knockdown

Using the cancer genome atlas (TCGA) data set and bioinformatics analyses, we identified miR-532-5p as a potential tumor suppressor in GC, and found that lncRNA LINC01410 might be a negative regulator of miR-532-5p. We then conducted a series of in vivo and in vitro assays to explore the effect of LINC01410 on miR-532-5p-mediated GC malignancy and the underlying mechanism involved.MiR-532-5p overexpression inhibited GC metastasis and angiogenesis in vitro and in vivo,whereas miR-532-5p silencing had the opposite effect. Further study showed that miR-532-5p attenuated NF-κB signaling by directly inhibiting NCF2 expression, while miR-532-5p silencing in GC enhanced NF-κB activity.Furthermore,we demonstrated miR-532-5p down-regulation was caused by aberrantly high expression of LINC01410 in GC.Mechanistically, overexpression of LINC01410 promoted GC angiogenesis and metastasis by binding to and suppressing miR-532-5p, which resulted in up-regulation of NCF2 and sustained NF-κB pathway activation.Interestingly, NCF2 could in turn increase the promoter activity and expression of LINC01410 via NF-κB, thus forming a positive feedback loop that drives the malignant behavior of GC.one of the most interesting findings from this study is that NF-κB can also regulate expression of LINC01410. Other studies have also reported the similar regulating mechanisms. For instance, lncRNA HCP5 up-regulates expression of Runt-related transcription factor 1 (RUNX1) in glioma cells, while overexpression of RUNX1 can also up-regulate HCP expression.