Minhang Hospital, Fudan University, Shanghai, China.
ICU, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, PuDong, Shanghai, China.
J Cell Biochem. 2020 Jan;121(1):313-321. doi: 10.1002/jcb.29176. Epub 2019 Jul 11.
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.
肺癌已被证实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）在癌症研究中受到了越来越多的关注。长链非编码 RNA（lncRNA）与多种癌症的发生和进展有关。然而，许多 lncRNA 在 LUAD 中尚未被彻底检测到。在这项研究中，通过生物信息学分析，我们发现锌指蛋白多型 2 反义 RNA 1（ZFPM2-AS1）与 LUAD 患者的预后不良有关。此外，ZFPM2-AS1 在 LUAD 组织和细胞中被检测到过表达。此外，ZFPM2-AS1 可以促进 LUAD 细胞的增殖。接下来，发现 miR-18b-5p 可以与 ZFPM2-AS1 结合并负调控其表达。miR-18b-5p 的靶基因 VMA21 可以与 miR-18b-5p 结合并受其负调控。更重要的是，ZFPM2-AS1 和 VMA21 都被发现与由 miR-18b-5p 和 Ago2 组成的 RNA 诱导沉默复合物结合。此外，ZFPM2-AS1 可以调节 VMA21 的表达。因此，ZFPM2-AS1 通过与 miR-18b-5p 竞争性结合来调节 VMA21 的表达。最后，挽救实验证实 ZFPM2-AS1 可以通过 miR-18b-5p/VMA21 轴调节 LUAD 细胞的增殖。
