Department of Oncology, Suqian First Hospital, Suqian, China.
Int J Exp Pathol. 2020 Dec;101(6):203-214. doi: 10.1111/iep.12366. Epub 2020 Sep 28.
Gastric cancer is a common and high-incidence malignant gastro-intestinal cancer that seriously threatens human life. Evidence suggests that microRNAs (miRNAs) play an essential role in regulating the occurrence and development of gastric cancer, but the possible mechanisms and effects remain to be further explored. In the present study, a new tumour suppresser function of miR-484 was identified in gastric cancer. The expression of miR-484 was obviously decreased, and the expression of CCL-18 was obviously increased in gastric cancer tissues and cell lines. In addition, upregulation of miR-484 suppressed cell proliferation, migration and invasion, and induced cell cycle arrest in G1 phase and cell apoptosis in gastric cancer cells. Besides, miR-484 mimics could block the PI3K/AKT signalling pathway. Moreover, CCL-18 was confirmed as a direct target of miR-484 by binding its 3'-UTR, and over-expression of CCL-18 could restore the effects of miR-484 on the growth and metastasis of gastric cancer. Finally, in vivo experiments showed that over-expression of miR-484 inhibited the subcutaneous tumorigenicity of gastric cancer cells, and the inhibition was blocked after over-expression of CCL-18. To conclude, miR-484 expression was downregulated in gastric cancer tissues and cells and played an anti-cancer role in the occurrence and development of gastric cancer, which may be achieved by inhibiting the expression of transcription factor CCL-18 and blocking the PI3K/AKT pathway.
胃癌是一种常见且高发的恶性胃肠癌，严重威胁人类生命。有证据表明，微小 RNA（miRNA）在调控胃癌的发生和发展中起着重要作用，但具体的机制和作用仍有待进一步探索。在本研究中，鉴定了 miR-484 在胃癌中的一个新的肿瘤抑制因子功能。miR-484 的表达在胃癌组织和细胞系中明显降低，CCL-18 的表达明显增加。此外，上调 miR-484 抑制了胃癌细胞的增殖、迁移和侵袭，并诱导细胞周期停滞在 G1 期和细胞凋亡。此外，miR-484 模拟物可以阻断 PI3K/AKT 信号通路。此外，CCL-18 通过结合其 3'UTR 被证实为 miR-484 的直接靶标，并且 CCL-18 的过表达可以恢复 miR-484 对胃癌生长和转移的影响。最后，体内实验表明，过表达 miR-484 抑制了胃癌细胞的皮下致瘤性，而 CCL-18 的过表达则阻断了这种抑制作用。总之，miR-484 在胃癌组织和细胞中的表达下调，并在胃癌的发生和发展中发挥抗癌作用，这可能是通过抑制转录因子 CCL-18 的表达和阻断 PI3K/AKT 通路来实现的。
