Copy number amplification-activated long non-coding RNA LINC00662 epigenetically inhibits BIK by interacting with EZH2 to regulate tumorigenesis in non-small cell lung cancer

Recently, studies have shown that lncRNAs play important roles in regulation of cancer cells proliferation, apoptosis and metastasis. Here, through systematic bioinformatics analysis and screening, we identified a long noncoding RNA LINC00662 with high copy number amplification in NSCLC. High expression of LINC00662 predicted a poorer survival. The exact sequence full-length of LINC00662 was determined by rapid amplification of cDNA ends (RACE). We also found that LINC00662 could regulate lung cancer cell proliferation both in vitro and in vivo. Mechanically, we obtained global expression profile that respond to LINC00662 knockdown through RNA-Seq analysis. And we found that LINC00662 could bind to EZH2 and recruit EZH2 to the promoter regions of BIK, regulating the level of H3K27me3 in the BIK promoter, thus epigenetically repressing BIK expression. Our results shown that lncRNA LINC00662, driven by copy number amplification, promotes tumorigenesis by EZH2/BIK cell axis, indicating that it was a potential molecular target of NSCLC.

Automated summary

Recent studies have shown that lncRNAs, such as LINC00662, play significant roles in the regulation of cancer cells proliferation, apoptosis, and metastasis. This study identified LINC00662 as a long noncoding RNA with high copy number amplification in NSCLC, and its high expression was associated with poor survival. Mechanistically, LINC00662 was found to interact with EZH2 and recruit it to the promoter regions of BIK, leading to epigenetic repression of BIK expression and promotion of tumorigenesis in lung cancer cells.