Department of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China.
Department of Respiratory and Critical Medicine, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China.
Biosci Rep. 2020 Feb 28;40(2). doi: 10.1042/BSR20200041.
As a zinc transporter, SLC39A7 (zip7) is vital in intestinal epithelial self-renewal, and recent studies suggested that SLC39A7 was related to cancer progression. Whereas, little is known about the role of SLC39A7 in gastric cancer (GC). In the present study, qRT-PCR analysis demonstrated that SLC39A7 mRNA level was increased in both GC tissues and cell lines. Overexpressing SLC39A7 boosted cell proliferation and migration, while inhibited apoptosis in GC. It was also found that si-SLC39A7 suppressed Akt/mTOR pathway and activation of Akt/mTOR pathway reversed the effects of si-SLC39A7 on GC development. Through prediction website, we found that SLC39A7 was directly regulated by miR-139-5p. miR-139-5p mimic had adverse effects on SLC39A7 expression and influence in the GC cell proliferation, migration and apoptosis by Akt/mTOR signaling pathway, while miR-139-5p inhibitor showed opposite effects. To conclude, our studies showed that SLC39A7 was negatively regulated by miR-139-5p. Besides, SLC39A7 positively regulated GC development through Akt/mTOR signaling pathway. These results indicate that SLC39A7 may be a candidate target gene for GC treatment.
作为锌转运蛋白，SLC39A7（zip7）在肠上皮细胞自我更新中至关重要，最近的研究表明 SLC39A7 与癌症进展有关。然而，SLC39A7 在胃癌（GC）中的作用知之甚少。在本研究中，qRT-PCR 分析表明 SLC39A7 mRNA 水平在 GC 组织和细胞系中均升高。过表达 SLC39A7 促进了 GC 细胞的增殖和迁移，而抑制了细胞凋亡。还发现 si-SLC39A7 抑制了 Akt/mTOR 通路，而 Akt/mTOR 通路的激活逆转了 si-SLC39A7 对 GC 发展的影响。通过预测网站，我们发现 SLC39A7 是由 miR-139-5p 直接调控的。miR-139-5p 模拟物对 SLC39A7 的表达和影响具有不利作用，通过 Akt/mTOR 信号通路影响 GC 细胞的增殖、迁移和凋亡，而 miR-139-5p 抑制剂则表现出相反的作用。总之，我们的研究表明 SLC39A7 受 miR-139-5p 的负调控。此外，SLC39A7 通过 Akt/mTOR 信号通路正向调节 GC 的发展。这些结果表明 SLC39A7 可能是 GC 治疗的候选靶基因。
