MicroRNA-20a Overexpression Inhibited Proliferation and Metastasis of Pancreatic Carcinoma Cells
MicroRNA-20a Overexpression Inhibited Proliferation and Metastasis of Pancreatic Carcinoma Cells
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MicroRNA-20a过表达抑制胰腺癌细胞增殖和转移
DOI：
10.1089/hum.2010.061
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发表时间：
2010-12-01
影响因子：
4.2
通讯作者：
Huang, Wenlin
中科院分区：
文献类型：
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作者：
Yan, Haijiao;Wu, Jiangxue;Huang, Wenlin
本研究的目的是探讨microRNA-20a对胰腺癌细胞增殖和侵袭的影响，为胰腺癌的治疗寻找新的有效策略。用原位杂交法检测了10例匹配的正常胰腺组织和胰腺癌组织中microRNA-20a的表达。应用实时荧光定量RT-PCR技术检测microRNA-20a在人胰腺癌细胞系BxPC-3和PANC-1及永生化人胰管上皮细胞系H6C7中的表达。体外和体内分析慢病毒介导的microRNA-20a过表达细胞的增殖和侵袭能力。此外，还研究了microRNA-20a对信号转导和转录激活蛋白3(STAT3)的调节作用，以阐明其可能的作用机制。稳定高表达microRNA-20a的胰腺癌细胞株(PANC-1和BxPC-3)在体内外的增殖和侵袭能力均低于亲本细胞或对照载体细胞。此外，我们发现microRNA-20a以剂量依赖的方式负调控STAT3蛋白的表达，而不改变Stat3mRNA的水平，并降低包含STAT3 3‘-非翻译区的荧光素酶报告结构的活性。这些结果表明，microRNA-20a在转录后水平调节STAT3，从而抑制细胞增殖和胰腺癌的侵袭。这可能为胰腺癌有效基因治疗的发展开辟新的视角。
The aim of this study was to investigate the effect of microRNA-20a on pancreatic carcinoma cell proliferation and invasion and to find a new effective treatment strategy for pancreatic carcinoma. MicroRNA-20a expression was determined in 10 matched normal pancreatic tissues and pancreatic carcinoma by in situ hybridization. Quantitative real-time RT-PCR was used to evaluate the expression of microRNA-20a in two pancreatic carcinoma cell lines (BxPC-3 and Panc-1) and immortal human pancreatic duct epithelial cell line H6C7. Proliferation and invasion capacity were analyzed for the cells with lentivirus-mediated overexpression of microRNA-20a both in vitro and in vivo. In addition, the regulation of signal transducer and activator of transcription proteins 3 (Stat3) by microRNA-20a was determined to elucidate the underlying mechanisms. The pancreatic cancer cell lines (Panc-1 and BxPC-3) stably overexpressing microRNA-20a showed reduced proliferation and invasion capacity in vitro and in vivo, compared with parental cells or cells transfected with a control vector. Furthermore, we found that microRNA-20a negatively regulated Stat3 protein expression in a dose-dependent manner without changing the Stat3mRNA level and decreased the activity of a luciferase reporter construct containing the Stat3 3'-untranslated region. These results show that microRNA-20a regulates Stat3 at the post-transcriptional level, resulting in inhibition of cell proliferation and invasion of pancreatic carcinoma. It may open a new perspective for the development of effective gene therapy for pancreatic carcinoma.