LINC00839 promotes colorectal cancer progression by recruiting RUVBL1/Tip60 complexes to activate NRF1

The long noncoding RNA LINC00839 has been shown to be involved in the progression of some cancer types, such as bladder cancer, prostate cancer, breast cancer, and neuroblastoma. However, if LINC00839 has roles in colorectal cancer (CRC), it has not been elucidated so far. Here, we focus on the biological role and involved mechanisms of LINC00839 in CRC. We show that LINC00839 is selectively upregulated in CRC and locates to the nucleus. High expression of LINC00839 is associated with poor outcomes in CRC patients. Functional experiments show that LINC00839 promotes CRC proliferation, invasion, and metastasis in vitro and in vivo. Mechanistically, LINC00839 recruits Ruvb1 to the Tip60 complex and increases its acetylase activity. LINC00839 guides the complex to the NRF1 promoter and promotes acetylation of lysines 5 and 8 of histones H4, thereby upregulating the expression of NRF1. Subsequently, NRF1 activates mitochondrial metabolism and biogenesis, thereby promoting CRC progression. In summary, our study reports on a mechanism by which LINC00839 positively regulates NRF1, thus promoting mitochondrial metabolism and biogenesis, as well as CRC progression.