Shi Jianping, Zhang Yi, Jin Nuyun, Li Yuqin, Wu Shengtian, Xu Leiming
Department of Digestion, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, P.R. China.
Department of Digestion, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
Oncol Res. 2017 Apr 14;25(4):523-536. doi: 10.3727/096504016X14756282819385. Epub 2016 Oct 5.
Gastric carcinoma is one of the most common malignancies in men, and microRNA plays a critical role in regulating the signaling networks of gastric carcinoma tumorigenesis and metastasis. We first report the functional characteristics of miR-221-3p in gastric carcinoma. Quantification in gastric carcinoma cell lines and tumor samples reveals significantly increasing miR-221-3p expression. Moreover, a high level of miR-221-3p is correlated with a poor prognosis for gastric carcinoma patients. Ectopic miR-221-3p expression significantly promotes gastric carcinoma cell proliferation, invasion, and sphere formation, while silencing miR-221-3p significantly inhibits these abilities in gastric carcinoma cells. Tests in vivo showed that miR-221-3p significantly promotes tumor growth in xenograft mouse models. In this study, we reveal that miR-221-3p targets PTEN mRNA and downregulates PTEN, which is the possible mechanism of miR-221-3p-induced oncogenic properties. Collectively, we reveal a critical role for miR-221-3p in gastric carcinoma development and progression.
胃癌是男性中最常见的恶性肿瘤之一,微小RNA在调节胃癌发生和转移的信号网络中起关键作用。我们首次报道了miR-221-3p在胃癌中的功能特性。对胃癌细胞系和肿瘤样本的定量分析显示miR-221-3p表达显著增加。此外,高水平的miR-221-3p与胃癌患者的不良预后相关。异位表达miR-221-3p显著促进胃癌细胞增殖、侵袭和球体形成,而沉默miR-221-3p则显著抑制胃癌细胞的这些能力。体内实验表明,miR-221-3p在异种移植小鼠模型中显著促进肿瘤生长。在本研究中,我们发现miR-221-3p靶向PTEN mRNA并下调PTEN,这可能是miR-221-3p诱导致癌特性的机制。总体而言,我们揭示了miR-221-3p在胃癌发生和发展中的关键作用。