The opposite role of alternatively spliced isoforms of LINC00477 in gastric cancer
The opposite role of alternatively spliced isoforms of LINC00477 in gastric cancer
复制标题
LINC00477 的选择性剪接异构体在胃癌中的相反作用
DOI：
10.2147/cmar.s202430
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Zhang, Xiefu
中科院分区：
文献类型：
--
作者：
Zhao, Hongchao;He, Yuanhang;Zhang, Xiefu
背景：转录本选择性剪接异常是与肿瘤发生密切相关的重要调控过程。目的：研究一种新的长链非编码RNA（lncRNA）LINC 00477在胃癌中的表型和功能。患者和方法：本研究采用Oncomine数据库中的140例胃癌标本和本院的17例胃癌标本，以及三种胃癌细胞系MKN-45、AGS和KATO III。测试LINC 00477的剪接同种型的表达。在体外和体内研究LINC 00477对胃癌的肿瘤作用。通过RIP和pull down实验进一步研究LINC 00477与乌头酸酶1（aconitase 1，ACO 1）的相互作用机制。结果：LINC 00477在胃癌组织中的表达水平低于正常胃组织。LINC 00477的亚型1在胃癌细胞中下调，而亚型2在胃癌细胞中上调。观察到异构体1和2在体外和体内癌细胞增殖和迁移中的相反作用。此外，确定LINC 00477的同种型1与ACO 1相互作用，并抑制ACO 1将柠檬酸盐转化为异柠檬酸盐的能力。结论：长链非编码RNA剪接异构体LINC 00477在胃癌发生中起重要作用。
Background: Aberrant transcript alternative splicing is an important regulatory process closely connected with oncogenesis. Purpose: The objective of this study was to determine the phenotype and function of a novel long noncoding RNA (lncRNA) LINC00477 in gastric cancer. Patients and methods: The gastric cancer samples of 140 from Oncomine database and 17 from our own hospital, as well as three gastric cancer cell lines MKN-45, AGS and KATO III were used in this study. The expression of the spliced isoforms of LINC00477 were tested. The tumor effects of LINC00477 on gastric cancer were investigated in vitro and in vivo. The mechanism of LINC00477 interacted with aconitase 1 (ACO1) was further examined by RIP and pull down assay. Results: The overall expression of LINC00477 was reduced in gastric cancers compared to normal gastric tissues. The isoform 1 of LINC00477 was down-regulated while the isoform 2 was up-regulated in gastric cancer cells. The opposite role of isoforms 1 and 2 in the proliferation and migration of cancer cells in vitro and in vivo was observed. Furthermore, isoform 1 of LINC00477 was determined to interact with ACO1 and suppress the conversion ability from citrate to isocitrate by ACO1. Conclusion: we presented the important roles of the spliced isoforms of long noncoding RNA, LINC00477 in gastric carcinogenesis.