Tumor-suppressive mir-663 gene induces mitotic catastrophe growth arrest in human gastric cancer cells
Tumor-suppressive mir-663 gene induces mitotic catastrophe growth arrest in human gastric cancer cells
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DOI：
10.3892/or_00000834
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发表时间：
2010-07-01
期刊：
影响因子：
4.2
通讯作者：
Ran, Yuliang
中科院分区：
文献类型：
--
作者：
Pan, Jian;Hu, Hai;Ran, Yuliang
越来越多的证据表明microRNA作为肿瘤抑制因子或癌基因参与了人类肿瘤的发生。越来越多的报告表明，人们对异常microRNA表达以及如何将其用于治疗包括癌症在内的人类疾病产生了兴趣。然而，其确切的生物学作用在很大程度上仍然未知。在本研究中，我们的目的是确定参与调节肿瘤生长的microRNA种类。通过进行定量逆转录-聚合酶链反应（RT-PCR）分析，我们证明了mir-663在人胃癌细胞系中下调，而不像在正常细胞中。将mir-663瞬时导入人胃癌细胞系BGC 823和SNU 5中，诱导这些细胞的形态学改变和增殖抑制。此外，mir-663改变肿瘤细胞中的DNA含量并诱导有丝分裂灾难的表型。此外，脂质体介导的mir-663递送抑制BGC 823和SNU 5细胞的体内生长。在引入mir-663后进行的蛋白质印迹分析揭示了用mir-663转染后细胞周期蛋白B的上调。我们的研究结果提供了证据表明，下调mir-663在肿瘤细胞中可能有助于异常细胞增生，导致胃癌的发展。因此，mir-663可能是一种有效的肿瘤生长抑制剂。
Increasing evidence suggests that microRNAs are involved in human carcinogenesis as tumor suppressors or oncogenes. A growing number of reports has shown that an interest has been sparked in aberrant microRNA expression and how they can be used to treat human diseases, including cancer. However, their precise biological role remains largely unknown. In the present study, we aimed to identify microRNA species involved in the regulation of tumor growth. By performing quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis, we demonstrated that mir-663 was downregulated in human gastric cancer cell lines unlike in normal cells. A transient introduction of mir-663 into the human gastric cancer cell lines BGC823 and SNU5 induced morphology changes and suppression of proliferation of these cells. In addition, mir-663 alters the DNA content and induces phenotypes of mitotic catastrophe in tumor cells. Moreover, the liposome-mediated delivery of mir-663 suppressed the in vivo growth of the BGC823 and SNU5 cells. Western blot analyses performed after the introduction of mir-663 revealed upregulation of cyclin B following transfection with mir-663. Our results provide evidence that downregulation of mir-663 in tumor cells may contribute to aberrant cell hyperplasia, leading to the development of gastric cancer. Therefore, mir-663 might function as a potent suppressor of tumor growth.