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Abstract：
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.
摘要：
肺癌已被证明是全球最常见的癌症之一。同时,作为肺癌的主要类型，肺腺癌（LUAD）在癌症研究中受到越来越多的关注。已知长链非编码RNA(lncRNA)与各种癌症的发生和进展有关。然而,许多lncRNAs尚未在LUAD中被彻底检测到。在这项研究中,通过生物信息学分析我们发现锌指蛋白multitype2反义RNA1(ZFPM2-AS1)与LUAD患者的不良预后相关。此外，在LUAD组织和细胞中检测到ZFPM2-AS1过表达。此外，ZFPM2-AS1可以促进LUAD细胞的增殖。接下来,发现miR-18b-5p与ZFPM2-AS1结合并被ZFPM2-AS1负调控。VMA21,miR-18b-5p的靶基因,可以与miR-18b-5p结合并被其负调控。更重要的是,发现ZFPM2-AS1和VMA21均与由miR-18b-5p和Ago2构建的RNA诱导沉默复合物连接。此外，ZFPM2-AS1可以调控VMA21的表达。因此,证实ZFPM2-AS1通过与miR-18b-5p竞争性结合来调节VMA21。最后,拯救试验证实ZFPM2-AS1可以通过miR-18b-5p/VMA21轴调节LUAD细胞增殖。
