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-7 miRNA的功能,并上调某些细胞周期相关基因如cyclin A、cyclin B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-7 miRNA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。
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 the differentiation and maturation of miRNA and by moderating the expression of some cell-cycle related genes. Lin28 has an important function in the tumor's tolerance of chemotherapy and radiotherapy. We review the physiological function of Lin28 in tumors and its function in tumor treatment.