Yang Jiebin, Lian Yikai, Yang Renzhi, Lian Yifan, Wu Jingtong, Liu Jingjing, Wang Keming, Xu Hongzhi
Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, P.R. China; Department of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, P.R. China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, P.R. China; School of Medicine, Xiamen University, Xiamen, Fujian, P.R. China.
Mol Ther Nucleic Acids. 2020 Mar 6;19:1164-1175. doi: 10.1016/j.omtn.2019.12.041. Epub 2020 Jan 15.
Non-protein-coding functional elements in the human genome in the postgenomic biology field have been drawing great attention in recent years. Thousands of long non-coding RNAs (lncRNAs) have been found to be expressed in various tumors. Yet only a small proportion of these lncRNAs have been well characterized. We have demonstrated that LINC00460 could affect cell proliferation through epigenetic regulation of KLF2 and CUL4A in human colorectal cancer. However, the clinical significance and biological role of LINC00460 in gastric cancer (GC) remain largely unknown. In this research, we discovered that LINC00460 is remarkably upregulated in GC tissues compared to the non-tumor tissues. Additionally, LINC00460 served as an independent prognostic marker in GC. Functionally, proliferation of GC cells could be regulated by LINC00460 both in vitro and in vivo. RNA sequencing (RNA-seq) analysis for the whole transcriptome indicated that LINC00460 may serve as a key regulatory factor in the tumorigenesis of GC. What's more, the biological function of LINC00460 was mediated, to certain extent, by the direct interaction with enhancer of zeste homolog 2 (EZH2) and lysine (K)-specific demethylase 1A (LSD1) proteins. Further analyses indicated that LINC00460 promoted GC proliferation at least partly through the downregulation of tumor suppressor-gene Cyclin G2 (CCNG2), which is mediated by EZH2 and LSD1. In conclusion, our results suggested that LINC00460 acted as an oncogene in GC to inhibit the expression of CCNG2 at least partly by binding with EZH2 and LSD1. Our study could provide additional insights into the development of novel target therapeutic methods for GC.
近年来，后基因组生物学领域中人类基因组的非蛋白质编码功能元件备受关注。人们发现，数千种长链非编码RNA（lncRNA）在各种肿瘤中表达。然而，这些lncRNA中只有一小部分得到了充分表征。我们已经证明，LINC00460可通过对人结肠癌中KLF2和CUL4A的表观遗传调控来影响细胞增殖。然而，LINC00460在胃癌（GC）中的临床意义和生物学作用仍 largely 未知。在本研究中，我们发现与非肿瘤组织相比，LINC00460在GC组织中显著上调。此外，LINC00460在GC中作为独立的预后标志物。在功能上，LINC00460在体外和体内均可调节GC细胞的增殖。对整个转录组的RNA测序（RNA-seq）分析表明，LINC00460可能是GC肿瘤发生中的关键调节因子。此外，LINC00460的生物学功能在一定程度上是由与zeste同源物2（EZH2）增强子和赖氨酸（K）特异性去甲基化酶1A（LSD1）蛋白的直接相互作用介导的。进一步分析表明，LINC00460至少部分通过由EZH2和LSD1介导的肿瘤抑制基因细胞周期蛋白G2（CCNG2）的下调来促进GC增殖。总之，我们的结果表明，LINC00460在GC中作为癌基因发挥作用，至少部分通过与EZH2和LSD1结合来抑制CCNG2的表达。我们的研究可为GC新型靶向治疗方法的开发提供更多见解。
