Long intergenic non-coding RNA 00473 promotes proliferation and migration of gastric cancer via the miR-16-5p/CCND2 axis and by regulating AQP3.
Long intergenic non-coding RNA 00473 promotes proliferation and migration of gastric cancer via the miR-16-5p/CCND2 axis and by regulating AQP3.
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长基因间非编码RNA 00473通过miR-16-5p/CCND2轴并通过调节AQP3促进胃癌的增殖和迁移
DOI：
10.1038/s41419-021-03775-9
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发表时间：
2021-05-15
影响因子：
9
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Zhuo S;Sun M;Bai R;Lu D;Di S;Ma T;Zou Z;Li H;Zhang Z
胃癌是世界范围内最常见的恶性肿瘤之一，但其发病机制尚不清楚。近年来越来越多的证据表明长链非编码RNA（longnoncodingRNAs，LncRNA）在多种肿瘤中发挥着重要作用。本研究旨在探讨长基因间非编码RNA 00473（LINC 00473）在胃癌中的功能。在本研究中，我们发现LINC 00473在肿瘤组织中的表达与配对的癌旁组织相比异常增加。LINC 00473在胃癌中的高表达与淋巴结转移风险、血管癌栓发生率和TNM分期相关。进一步的实验表明，LINC 00473的过表达在体内外均能促进胃癌细胞的增殖和转移。随着LINC 00473浓度的降低，胃癌细胞凋亡率明显增加。在机制上，LINC 00473可以在细胞质中海绵化miR-16- 5 p并解除其对CCND 2的抑制。此外，通过RNA转录组测序发现，AQP 3是LINC 00473的重要下游靶基因，如通过qRT-PCR和western blot所证明的。过表达LINC 00473可部分逆转AQP 3表达减少对胃癌细胞增殖和转移的影响。Western blot证实LINC 00473通过CREB调节AQP 3的表达。我们的研究表明LINC 00473/miR-16- 5 p/CCND 2轴在胃癌的增殖中发挥作用，并通过调节AQP 3影响胃癌细胞的转移，使其成为胃癌潜在的治疗靶点。
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.