Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
GenoArray Biotech, Suzhou, China.
Int J Biol Sci. 2018 Apr 30;14(6):644-653. doi: 10.7150/ijbs.25272. eCollection 2018.
Gastric cancer (GC) is one of the most common malignancies with high mortality rate. MiR-152 may exert the function of tumor suppressor by regulating its target gene, including PIK3CA. Nevertheless, all of the described functions are referred explicitly to miR-152-3p, while miR-152-5p as a passenger strand is poorly realized and entirely ignored. We previously selected miR-152-5p as a candidate using cell migration inhibition screening for GC cells and predicted that miR-152-5p might also target PIK3CA. In this study, we found an abnormal proportion of miR-152-3p / miR-152-5p in GC (gastric cancer) tissues and cells and demonstrated that miR-152-5p had poorer stability in GC cells, revealing the possibility that miR-152-5p is abnormally "suppressed" in gastric cancer. We also investigated and confirmed the role of miR-152-5p in GC by a series of experiments, and found that miR-152-5p modulated cell viability, migration, invasion, and cell-cycle progression of human GC cells, and also inhibited tumor growth and metastasis partially by targeting PIK3CA. More interestingly, it was proved that miR-152-3p and miR-152-5p had synergistic effects on the inhibition of PIK3CA in GC cells. The results of this study suggest that miR-152-5p may act as a tumor suppressor in SGC-7901 gastric cancer cells via targeting PIK3CA. Further, the study provides a novel insight into the roles of miRNA* during carcinogenesis.
胃癌(GC)是一种常见的高死亡率恶性肿瘤。miR-152 可能通过调节其靶基因,包括 PIK3CA,发挥肿瘤抑制作用。然而,所有描述的功能都明确指的是 miR-152-3p,而作为过客链的 miR-152-5p 则被理解得很差,完全被忽视了。我们之前使用细胞迁移抑制筛选法从 GC 细胞中选择 miR-152-5p 作为候选物,并预测 miR-152-5p 也可能靶向 PIK3CA。在这项研究中,我们发现 GC(胃癌)组织和细胞中 miR-152-3p/miR-152-5p 的比例异常,并证明 GC 细胞中 miR-152-5p 的稳定性较差,这表明 miR-152-5p 在胃癌中可能异常“受抑制”。我们还通过一系列实验研究并证实了 miR-152-5p 在 GC 中的作用,发现 miR-152-5p 调节人 GC 细胞的细胞活力、迁移、侵袭和细胞周期进程,并通过靶向 PIK3CA 部分抑制肿瘤生长和转移。更有趣的是,研究证明 miR-152-3p 和 miR-152-5p 在抑制 GC 细胞中的 PIK3CA 方面具有协同作用。这项研究的结果表明,miR-152-5p 可能通过靶向 PIK3CA 在 SGC-7901 胃癌细胞中发挥肿瘤抑制作用。此外,该研究为 miRNA* 在癌变过程中的作用提供了新的见解。