Lin28信号通路与肿瘤.pdfVIP

530 中国肿瘤临床2014年第41卷第8期 Chin J Clin Oncol 2014,Vol.41,No.8 · · 国家基金研究进展综述 Lin28信号通路与肿瘤* ① ② ① ① 荚耘路 吕可真 林 娜 胡文献 摘要 Lin28是一种结构上高度保守的RNA结合蛋白，其在机体正常生长发育代谢及某些疾病状态，如肿瘤发生发展中有 重要作用。近年的研究发现，Lin28在机体中的过表达能够抑制let-7miRNA的功能，并上调某些细胞周期相关基因如cyclinA、 cyclinB等的表达，从而促进干细胞的增殖。在人类恶性肿瘤细胞中，Lin28的激活能选择性地阻断原始let-7miRNA的加工成 熟并最终促进肿瘤的发生；Lin28在肿瘤疾病进程中的其他作用机制包括：通过抑制肿瘤相关microRNA的分化成熟、上调细胞 周期相关基因的表达影响肿瘤的发展及预后。另外，Lin28在肿瘤放化疗耐受相关研究中的重要作用日益凸显。为此，本文对 Lin28的相关生理功能和其在肿瘤发生发展的相关机制及治疗前景做一综述。 关键词 Lin28 miRNA 肿瘤 治疗 doi:10.3969/j.issn.1000-8179 The signal pathway of Lin28 and tumor 1 2 1 1,2 Yunlu JIA , Kezhen LV , Na LIN , Wenxian HU Correspondence to: Wenxian HU; E-mail: hwx2206@ 1Department of Surgical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China; 2Department of General Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310004, China This work was supported by the National Natural Science Foundation of China (No: and Qianjiang Talents Scheme (No: 2010R 10065) Abstract Lin28 is a highly conserved RNA-binding protein that has an important role in human body development, metabolism, and tumorigenesis. Previous studies have found that the activation of Lin28 can suppress the maturity of let-7 miRNA in stem cells and promote the proliferation of stem cells by upregulating cell-cycle related genes, such as cyclins A and B. Other mechanisms underlying the activation of Lin28 can selectively block the processes of pre-let-7 miRNA in embryonic stem cells and ultimately promote tumori- genesis. In addition, Lin28 affects the occurrence, development, and prognosis of cancer by inhibiting