Department of Pulmonary and Critical Care Medicine, The First People's Hospital of Wenling, Wenling, Zhejiang, China.
Department of Pediatrics, The First People's Hospital of Wenling, Wenling, Zhejiang, China.
Cell Biol Int. 2020 Dec;44(12):2438-2449. doi: 10.1002/cbin.11451. Epub 2020 Oct 7.
Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. The abnormal expression of long noncoding RNAs (lncRNAs) can facilitate or suppress the development of malignant tumors. lncRNA actin alpha 2, smooth muscle antisense RNA 1 (ACTA2-AS1) has been reported to function as a tumor suppressor in liver cancer, nevertheless, its influences on LUAD remain to be investigated. In this paper, ACTA2-AS1 was identified as a downregulated lncRNA in LUAD samples and cells. Functionally, ACTA2-AS1 overexpression restrained cell proliferation but accelerated cell apoptosis in LUAD. In addition, we determined the suppressive effect of ACTA2-AS1 on LUAD cell invasion, migration, and epithelial-mesenchymal transition progress. Mechanistically, ACTA2-AS1 exert functions as a competing endogenous RNA through serving as a sponge for microRNA-378a-3p (miR-378a-3p) and microRNA-4428 (miR-4428) to elevate SRY-related high-mobility group box 7 (SOX7) expression. Importantly, SOX7 silencing could recover the ACTA2-AS1-mediated cell functions. To summarize, ACTA2-AS1 suppresses the malignant processes of LUAD cells through sequestering miR-378a-3p and miR-4428 to augment SOX7 expression.
肺腺癌（LUAD）是肺癌最常见的组织学亚型。长链非编码 RNA（lncRNA）的异常表达可以促进或抑制恶性肿瘤的发展。已有研究报道，lncRNA 肌动蛋白α 2，平滑肌反义 RNA 1（ACTA2-AS1）在肝癌中作为肿瘤抑制因子发挥作用，但它对 LUAD 的影响仍有待研究。在本文中，ACTA2-AS1 被鉴定为 LUAD 样本和细胞中下调的 lncRNA。功能上，ACTA2-AS1 的过表达抑制了 LUAD 细胞的增殖，但加速了细胞凋亡。此外，我们确定了 ACTA2-AS1 对 LUAD 细胞侵袭、迁移和上皮-间充质转化过程的抑制作用。机制上，ACTA2-AS1 通过作为 microRNA-378a-3p（miR-378a-3p）和 microRNA-4428（miR-4428）的海绵，发挥竞争性内源 RNA 的功能，从而提高 SRY 相关高迁移率族盒 7（SOX7）的表达。重要的是，SOX7 的沉默可以恢复 ACTA2-AS1 介导的细胞功能。总之，ACTA2-AS1 通过结合 miR-378a-3p 和 miR-4428 抑制 SOX7 的表达，从而抑制 LUAD 细胞的恶性进程。
