LncRNA LINC00839 promotes colorectal cancer progression by RUVBL1/Tip60-NRF1 signaling pathway

Purpose: we focused on the biological roles and mechanism of the lncRNA LINC00839 in CRC. Methods: In situ hybridization (ISH), and quantitative real-time PCR (qPCR) were used to detect the expression of LINC00839 in paired CRC specimen. Biological function of LINC00839 was determined in vitro and in vivo. Western blot, bioinformatics analysis, RNA pull-down, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation assays (ChIP) were performed to identify the mechanisms underlying the functions of LINC00839 in CRC. Results: We found that LINC00839 was located in the nucleus of CRC cells and that LINC00839 was upregulated in CRC. High expression of LINC00839 was associated with poor outcome in CRC patients. Functionally, upregulation of LINC00839 promoted CRC cell proliferation, invasion, and metastasis in vitro and in vivo. Mechanistic investigations revealed that LINC00839 can promote the acetylation of histones H4K5 and H4K8 at the promoter of NRF1 after recruiting the RUVBL1/Tip60 complex, thereby upregulating the expression of NRF1. Subsequently, NRF1 served as an activator in mitochondrial metabolism and biogenesis, which, in turn, promoted CRC progression. Overall design: overexpressing LINCRNA CRC compared with control cell Transcriptomes