Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou road, 210029, Nanjing, Jiangsu Province, China.
Department of Pathology, Zhejiang Provincial People's Hospital & People's Hospital of Hangzhou Medical College, 310014, Hangzhou, Zhejiang Province, China.
Cell Death Dis. 2021 May 15;12(5):496. doi: 10.1038/s41419-021-03775-9.
Gastric cancer (GC) is one of the most common malignancies worldwide, but its molecular mechanisms remain unclear. Increasing evidence indicates that long non-coding RNAs (LncRNAs) play a pivotal role in various cancers recently. Our present study focused on exploring the function of long intergenic non-coding RNA 00473 (LINC00473) in GC. In this study, we found that LINC00473 expression was aberrantly increased in tumor tissues compared with the paired para-cancerous tissues. The expression of high LINC00473 in GC was notably correlated with a higher risk of lymphatic metastasis, a higher incidence of vascular cancer embolus, and advanced TNM stage. Further experiments showed that the overexpression of LINC00473 could promote the proliferation and metastasis of GC cells both in vitro and in vivo. The apoptosis of GC cells increased significantly by the decrease of LINC00473. Mechanistically, LINC00473 could sponge miR-16-5p in the cytoplasm and relieve its suppression of CCND2. Moreover, AQP3 was found to be a significant downstream target gene for LINC00473 through RNA transcriptome sequencing, as demonstrated by qRT-PCR and western blot. Overexpression of LINC00473 can partially reverse the effects of AQP3 decrease on GC proliferation and metastasis. LINC00473 regulated AQP3 expression through CREB was confirmed by western blot. Our research indicates that LINC00473/miR-16-5p/CCND2 axis plays a role in the proliferation of GC and modulates AQP3 to influence GC cell metastasis, making it a potential therapeutic target for GC.
胃癌（GC）是世界上最常见的恶性肿瘤之一，但其分子机制仍不清楚。越来越多的证据表明，长链非编码 RNA（lncRNAs）最近在各种癌症中发挥着关键作用。我们目前的研究集中在探索长链非编码 RNA 00473（LINC00473）在 GC 中的功能。在本研究中，我们发现 LINC00473 在肿瘤组织中的表达与配对的癌旁组织相比异常增加。GC 中高 LINC00473 的表达与更高的淋巴转移风险、更高的血管癌栓发生率和更晚期的 TNM 分期显著相关。进一步的实验表明，LINC00473 的过表达可以促进 GC 细胞在体外和体内的增殖和转移。LINC00473 的减少显著增加了 GC 细胞的凋亡。从机制上讲，LINC00473 可以在细胞质中海绵吸附 miR-16-5p，并减轻其对 CCND2 的抑制作用。此外，通过 RNA 转录组测序发现 AQP3 是 LINC00473 的一个显著下游靶基因，qRT-PCR 和 Western blot 也验证了这一点。过表达 LINC00473 可以部分逆转 AQP3 减少对 GC 增殖和转移的影响。Western blot 证实，LINC00473 通过 CREB 调节 AQP3 的表达。我们的研究表明，LINC00473/miR-16-5p/CCND2 轴在 GC 的增殖中起作用，并调节 AQP3 影响 GC 细胞转移，使其成为 GC 的潜在治疗靶点。
