LINC00839 promotes colorectal cancer progression by recruiting RUVBL1/Tip60 complexes to activate NRF1
LINC00839 promotes colorectal cancer progression by recruiting RUVBL1/Tip60 complexes to activate NRF1
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DOI：
10.15252/embr.202154128
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发表时间：
2022-07-25
期刊：
影响因子：
7.7
通讯作者：
Zhou, Jun
中科院分区：
文献类型：
--
作者：
Liu, Xiaoting;Chen, Jianxiong;Zhou, Jun
长链非编码RNA LINC00839已被证明参与某些癌症类型的进展，如膀胱癌、前列腺癌、乳腺癌和神经母细胞瘤。然而，LINC00839是否在结直肠癌（CRC）中具有作用，迄今为止尚未阐明。在此，我们重点介绍LINC00839在CRC中的生物学作用和相关机制。我们发现LINC00839在CRC中选择性上调并定位于细胞核。LINC00839的高表达与CRC患者的不良结局相关。功能实验显示LINC00839在体外和体内促进CRC增殖、侵袭和转移。在机制上，LINC00839将Ruvb1募集到Tip60复合物中并增加其乙酰化酶活性。LINC00839将复合物引导至NRF1启动子并促进组蛋白H4的赖氨酸5和8的乙酰化，从而上调NRF1的表达。随后，NRF1激活线粒体代谢和生物发生，从而促进CRC进展。总之，我们的研究报告了LINC00839积极调节NRF1的机制，从而促进线粒体代谢和生物发生以及CRC进展。
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.