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基因修饰（敲除、变异和过度表达）小鼠自90年代初应用于心脏学研究。近十余年来,利用这一类模型的研究发现对心血管领域所取得的重要进展有着突出的贡献,已经成为该领域里具有举足轻重地位的研究手段。目前,基因修饰小鼠模型的数量日益增多并已形成系统,有关的心脏表现型数据库日趋丰富,多种从整体到分子水平的表现型的研究手段已十分成熟。在今后的心脏研究中,小鼠模型有望对阐明疾病的分子机制和探索新的治疗途径起到很大的推动作用。

Previous studies have shown that the expression of microRNA-4458 （miR-4458） is dysregulated in hepatocellular carcinoma and colon cancer. In this study, we investigated the direct target of miR-4458 and its biological functions in human lung cancer ceils. By using the database TargetScan, we identified Lin28B, an oncogene, as a direct target gene of miR-4458. In dual-lucJferase reporter assay, we found that miR-4458 mimics dose-dependently inhibited the luciferase activity of the wild-type 3＇UTR of Lin28B in human lung cancer A549 and NCi-H1299 cell lines without affecting its mutant forms, whereas anti-miR-4458, an inhibitor of miR-4458, dose-dependently promoted the luciferase activity of the wild-type 3＇UTR of Lin28B in A549 and NCI-H1299 cell lines without affecting its mutant forms. Overexpression of miR-4458 significantly decreased the protein levels of Lin28B in the cells, and inhibited the cell growth and colony formation. Conversely, knockdown of miR-4458 with anti-miR-4458 significantly increased the protein levels of Lin28B, and promoted the cell proliferation, which could be reverted by knockdown of Lin28B expression. In addition, we detected the expression of Lin28B using RT-PCR in 40 human lung cancer tissues and matched peritumoral tissues, and found that Lin28B was overexpressed in lung cancer tissues and negatively correlated with miR-4458 expression （r=-0.694, P〈0.05）. We conclude that miR-4458 is a tumor suppressor, and Lin28B is the direct target of miR-4458. These results suggest the modulation of miR-4458/Lin28B expression offers a potential therapeutic strategy for lung cancer.

目的 探讨Ｐ７３基因转录表达与肺癌发生、发展的关系。方法 采用逆转录多聚酶链反应技术（ＲＴ－ＰＣＲ）检测３２例非小细胞肺组织、癌组织和７例肺良性病变组织，及其对应正常肺组织Ｐ７３ｍ，ＲＮＡ的表达。结果 ３２例肺癌组织中２８例Ｐ７３表达明显升高，肺７癌组织Ｐ７３ｍＲＮＡ阳性表达率明显高于癌旁肺组织和肺良性病变组织（Ｐ〈０．０１）。肺癌组织强Ｐ７３ｍＲＮＡ阳性表达率型、细胞分化程度和Ｐ－ＴＮＭ分期无明