lncRNA ZFPM2-AS1 promotes proliferation via miR-18b-5p/VMA21 axis in lung adenocarcinoma
lncRNA ZFPM2-AS1 promotes proliferation via miR-18b-5p/VMA21 axis in lung adenocarcinoma
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DOI：
10.1002/jcb.29176
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发表时间：
2019-07-11
影响因子：
4
通讯作者：
Gao, Xiwen
中科院分区：
文献类型：
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作者：
Xue, Min;Tao, Weimin;Gao, Xiwen
肺癌已被证明是地球仪最常见的癌症之一。同时，作为肺癌的主要类型，肺腺癌（LUAD）在肿瘤研究中受到越来越多的关注。已知长链非编码RNA（lncRNA）与多种癌症的发生和进展相关。然而，许多lncRNA在LUAD中尚未被彻底检测到。本研究通过生物信息学分析发现锌指蛋白2型反义RNA 1（ZFPM 2-AS 1）与LUAD患者预后不良相关。此外，检测到ZFPM 2-AS 1在LUAD组织和细胞中过表达。ZFPM 2-AS 1能促进LUAD细胞的增殖。接下来，发现miR-18 b-5 p与ZFPM 2-AS 1结合并受ZFPM 2-AS 1负调控。miR-18 b-5 p的靶基因VMA 21可与miR-18 b-5 p结合并受其负调控。更重要的是，发现ZFPM 2-AS 1和VMA 21都附着于由miR-18 b-5 p和Ago 2构建的RNA诱导的沉默复合物。ZFPM 2-AS 1对VMA 21的表达具有调节作用。因此，证实ZFPM 2-AS 1通过与miR-18 b-5 p竞争性结合来调节VMA 21。最后，拯救实验证实ZFPM 2-AS 1可以通过miR-18 b-5 p/VMA 21轴调节LUAD细胞增殖。
Lung cancer has been proved to be one of the most common kinds of cancers around the globe. Meanwhile, as the predominant type of lung cancer, lung adenocarcinoma (LUAD) has received increasing attention in cancer research. Long noncoding RNAs (lncRNAs) are known to be associated with oncogenesis and progression of various cancers. However, many lncRNAs have not been thoroughly detected in LUAD. In this study, through bioinformatics analysis we found that zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) was associated with poor prognosis of LUAD patients. Also, ZFPM2-AS1 was detected to be overexpressed in LUAD tissues and cells. Furthermore, ZFPM2-AS1 could promote the proliferation of LUAD cells. Next, miR-18b-5p was found to bind with and negatively regulated by ZFPM2-AS1. VMA21, target gene of miR-18b-5p, could bind with and be negatively regulated by miR-18b-5p. More importantly, both ZFPM2-AS1 and VMA21 were found to be attached to the RNA-induced silencing complex constructed from miR-18b-5p and Ago2. Also, ZFPM2-AS1 could regulate the expression of VMA21. Therefore, ZFPM2-AS1 were confirmed to regulate VMA21 by competitively binding with miR-18b-5p. Finally, rescue assays confirmed that ZFPM2-AS1 could regulate LUAD cell proliferation via miR-18b-5p/VMA21 axis.