The Comprehensive Cancer Center of Drum Tower Hospital, Nanjing Medical University, Zhongshan Road 321, Nanjing 210008, People's Republic of China.
Med Oncol. 2012 Jun;29(2):886-92. doi: 10.1007/s12032-011-9862-7. Epub 2011 Feb 24.
Aberrant expression of microRNA-146a (miR-146a) has been reported to be involved in development and progression in various types of cancers, but its role in gastric cancer has not been fully elucidated. The purpose of this study was to investigate the levels of miR-146a expression and its function in human gastric cancer. Quantitative real-time polymerase chain reaction was used to detect the levels of miR-146a expression in gastric cancer tissue samples and cell lines. The cell growth rate of MKN-45 gastric cancer cells transfected with miR-146a mimics was examined by MTT assay. The effects of miR-146a on cell cycle and apoptosis were assessed by FACS analyses in MKN-45 cells. Thirty-six of 43 gastric cancer tissue samples (84%) showed decreased expression of miR-146a. We found low expression of miR-146a was correlated with increased tumor size (P = 0.006) and poor differentiation (P = 0.010) in gastric cancer. Overall survival time of patients with high miR-146a expression was significantly longer than that of patients with low expression of miR-146a (P = 0.011). The MTT assay showed that introduction of miR-146a inhibited cell proliferation in MKN-45 cells (P < 0.05). The proportion of apoptotic cells induced by transfection of miR-146a mimics were greater than that induced by transfection of the negative control mimics (11.9 vs. 5.9%). Our results suggested that miR-146a has potential as a novel suppressor gene in gastric cancer and its down-regulation may promote the progression of gastric cancer.
miR-146a 的异常表达已被报道参与多种类型癌症的发生和发展，但它在胃癌中的作用尚未完全阐明。本研究旨在探讨 miR-146a 在人胃癌中的表达水平及其功能。采用实时定量聚合酶链反应检测胃癌组织样本和细胞系中 miR-146a 的表达水平。通过 MTT 试验检测转染 miR-146a 模拟物的 MKN-45 胃癌细胞的细胞生长率。通过 FACS 分析评估 miR-146a 对 MKN-45 细胞周期和凋亡的影响。43 例胃癌组织样本中的 36 例（84%）表现出 miR-146a 的表达下调。我们发现 miR-146a 的低表达与胃癌肿瘤大小增大（P=0.006）和分化不良（P=0.010）相关。miR-146a 高表达患者的总生存时间明显长于 miR-146a 低表达患者（P=0.011）。MTT 试验表明，miR-146a 的引入抑制了 MKN-45 细胞的增殖（P<0.05）。转染 miR-146a 模拟物诱导的凋亡细胞比例大于转染阴性对照模拟物诱导的凋亡细胞比例（11.9%比 5.9%）。我们的结果表明，miR-146a 可能是胃癌中的一种新型抑癌基因，其下调可能促进胃癌的进展。
