LINC00662 promotes hepatocellular carcinoma progression via altering genomic methylation profiles
LINC00662 promotes hepatocellular carcinoma progression via altering genomic methylation profiles
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LINC00662 通过改变基因组甲基化谱促进肝细胞癌进展。
DOI：
10.1038/s41418-020-0494-3
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发表时间：
2020-01-20
影响因子：
12.4
通讯作者：
Li, Zhen
中科院分区：
文献类型：
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作者：
Guo, Tao;Gong, Cheng;Li, Zhen
鉴定存活相关的长链非编码rna （lncRNAs）是发现肝细胞癌（HCC）治疗方法的一种手段。此外，异常的全基因组低甲基化与HCC的发生和发展有关。然而，lncRNA失调与全基因组低甲基化在肝癌发生中的关系尚未完全阐明。一种名为LINC00662的新型lncRNA先前被证明在胃肠道癌症中发挥作用。在这项研究中，我们证明了这种lncRNA在体外和体内都与生存相关，并表现出致癌特性。此外，我们确定LINC00662可以通过同步降低s -腺苷蛋氨酸（SAM）水平和提高s -腺苷同型半胱氨酸（SAH）水平导致全基因组低甲基化并改变基因组甲基化谱。机制上，LINC00662被确定通过RNA-RNA和rna -蛋白相互作用调节影响SAM和SAH水平的关键酶，即蛋氨酸腺苷转移酶1A （MAT1A）和s -腺苷同型半胱氨酸水解酶（AHCY）。此外，我们证明了一些SAM依赖的hcc促进基因可以通过LINC00662通过MAT1A/SAM和AHCY/SAH的LINC00662偶联轴改变其启动子的甲基化状态而被LINC00662调控。综上所述，本研究的结果表明，LINC00662可能是HCC治疗的潜在生物标志物。更重要的是，我们提出了lncRNA在调节基因组甲基化以促进癌基因激活中的新作用。
The identification of viability-associated long noncoding RNAs (lncRNAs) is a means of uncovering therapeutic approaches for hepatocellular carcinoma (HCC). In addition, aberrant genome-wide hypomethylation has been implicated in HCC initiation and progression. However, the relationship between lncRNA dysregulation and genome-wide hypomethylation in hepatocarcinogenesis has not been fully elucidated. A novel lncRNA named LINC00662 was previously demonstrated to play a role in gastrointestinal cancer. In this study, we demonstrated that this lncRNA was correlated with survival and exhibited oncogenic properties, both in vitro and in vivo. Moreover, we determined that LINC00662 could lead to genome-wide hypomethylation and alter the genomic methylation profile by synchronously reducing the S-adenosylmethionine (SAM) level and enhancing the S-adenosylhomocysteine (SAH) level. Mechanistically, LINC00662 was determined to regulate the key enzymes influencing SAM and SAH levels, namely, methionine adenosyltransferase 1A (MAT1A) and S-adenosylhomocysteine hydrolase (AHCY), by RNA-RNA and RNA-protein interactions. In addition, we demonstrated that some SAM-dependent HCC-promoting genes could be regulated by LINC00662 by altering the methylation status of their promoters via the LINC00662-coupled axes of MAT1A/SAM and AHCY/SAH. Taken together, the results of this this study indicate that LINC00662 could be a potential biomarker for HCC therapy. More importantly, we proposed a new role of lncRNA in regulating genomic methylation to promote oncogene activation.