Pan Tao, Chen Wenjun, Yuan Xiaoming, Shen Jun, Qin Chuan, Wang Linbo
Department of Surgical Oncology Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou China.
FEBS Open Bio. 2017 May 24;7(7):905-914. doi: 10.1002/2211-5463.12215. eCollection 2017 Jul.
MicroRNAs (miRNAs) are reported to play vital roles in tumor progression. Recently, miR-944 was reported to play either an oncogenic or tumor suppressive role in human cancers. However, the expression of miR-944 and its exact role in gastric cancer (GC) remain unknown. This study aimed to evaluate whether loss of miR-944 could promote the epithelial-mesenchymal transition (EMT) of GC. Reduced expression of miR-944 was identified in 40 pairs of human GC and matched normal tissues by qRT-PCR. Reduced expression of mi-944 was also observed in GC cell lines. Restoration of miR-944 inhibited cell migration and invasion in MGC-803 cells, while its loss facilitated metastasis of SGC-7901 and BGC-823 cells. Notably, miR-944 overexpression prohibited EMT of GC cells , while miR-944 knockdown had the opposite effect. Bioinformatics software predicted that MACC1 was a direct target of miR-944. We observed negative regulation of miR-944 on MACC1 expression, and direct binding between miR-944 and MACC1 was verified by dual-luciferase assays in HEK293T cells. Restoration of MACC1 resulted in promoted EMT and metastasis in miR-944-overexpressing MGC-803 cells. Loss of MACC1 abrogated the effects of miR-944 knockdown on EMT and metastasis of SGC-7901 cells. We also found that the Met-AKT pathway might be involved in MACC1-mediated EMT. In conclusion, miR-944 acts as an inhibitor of EMT and metastasis of GC by targeting MACC1. This study highlights the potential effects of miR-944 in the prognosis and treatment of GC.
据报道，微小RNA（miRNA）在肿瘤进展中发挥着至关重要的作用。最近，有报道称miR-944在人类癌症中发挥致癌或抑癌作用。然而，miR-944在胃癌（GC）中的表达及其确切作用仍不清楚。本研究旨在评估miR-944缺失是否会促进GC的上皮-间质转化（EMT）。通过qRT-PCR在40对人GC及其配对的正常组织中鉴定出miR-944表达降低。在GC细胞系中也观察到mi-944表达降低。miR-944的恢复抑制了MGC-803细胞的迁移和侵袭，而其缺失则促进了SGC-7901和BGC-823细胞的转移。值得注意的是，miR-944过表达抑制了GC细胞的EMT，而miR-944敲低则产生相反的效果。生物信息学软件预测MACC1是miR-944的直接靶点。我们观察到miR-944对MACC1表达的负调控，并通过HEK293T细胞中的双荧光素酶测定验证了miR-944与MACC1之间的直接结合。MACC1的恢复导致miR-944过表达的MGC-803细胞中EMT和转移增加。MACC1的缺失消除了miR-944敲低对SGC-7901细胞EMT和转移的影响。我们还发现Met-AKT通路可能参与MACC1介导的EMT。总之，miR-944通过靶向MACC1作为GC的EMT和转移抑制剂。本研究突出了miR-944在GC预后和治疗中的潜在作用。
