The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Biomed Pharmacother. 2018 May;101:406-413. doi: 10.1016/j.biopha.2018.02.104. Epub 2018 Mar 22.
Gastric cancer incidence is relatively higher in China than that in developed countries; however, molecular mechanisms considering the initiation and progression of gastric cancer are still unclear. For decades, numerous microRNAs have been found to regulate a wide range of biological functions in gastric cancer. However, the oncogenic function of miR-615-3p in gastric cancer has not been reported to date. With the help of gene and microRNA chips in 10 patients, we were able to screen differential expressed genes and microRNAs compared with normal gastric tissues. After that, online bioinformatics analysis tools were used to predict microRNAs' potential targets. As a result, miR-615-3p and its potential target, CELF2, were selected for further experiments. QRT-PCR and western blot results indicated the aberrant high expression of miR-615-3p and low expression of CELF2 in gastric cancer both in vivo and in vitro. Moreover, miR-615-3p expression correlated to T and M stage. Up regulation of miR-615-3p inhibited the apoptosis, promoted proliferation and migration and led to the down-regulation of CELF2. Meanwhile, down-regulation of miR-615-3p resulted in anti-tumor effects. Immunochemistry staining of CELF2 showed its association with T, N and M stage. In addition, overexpression of CELF2 could reverse miR-615-3p's oncogenic functions stated before. These findings indicate that miR-615-3p promotes gastric cancer proliferation and migration by suppressing CELF2 expression for the first time, providing clues for future clinical practices.
在中国，胃癌的发病率相对高于发达国家；然而，考虑到胃癌的发生和发展的分子机制仍不清楚。几十年来，已经发现许多 microRNAs 可以调节胃癌中的广泛的生物学功能。然而，miR-615-3p 在胃癌中的致癌功能迄今尚未报道。在 10 名患者的基因和 microRNA 芯片的帮助下，我们能够筛选出与正常胃组织相比差异表达的基因和 microRNAs。之后，使用在线生物信息学分析工具来预测 microRNAs 的潜在靶标。结果，选择 miR-615-3p 和其潜在靶标 CELF2 进行进一步实验。QRT-PCR 和 western blot 结果表明，miR-615-3p 在体内和体外的胃癌中表达异常升高，而 CELF2 表达降低。此外，miR-615-3p 的表达与 T 和 M 期相关。miR-615-3p 的上调抑制了细胞凋亡，促进了增殖和迁移，并导致 CELF2 的下调。同时，下调 miR-615-3p 则产生抗肿瘤作用。CELF2 的免疫组织化学染色表明其与 T、N 和 M 期有关。此外，CELF2 的过表达可以逆转之前提到的 miR-615-3p 的致癌作用。这些发现表明，miR-615-3p 通过抑制 CELF2 的表达首次促进胃癌的增殖和迁移，为未来的临床实践提供了线索。
