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作为一个关键的异时性基因(heterochronic gene)家族成员蛋白,Lin28及其同源分子Lin28B在原始生殖细胞(PGCs)发生、生殖细胞肿瘤(GCTs)恶化和性发育成熟过程中发挥着重要的调控作用。Lin28不但可与let-7 miRNA家族的前体终末环相结合,从而阻断let-7miRNA的成熟过程,而且可诱导let-7前体尿苷化和降解。同时,Lin28也可选择性地结合mRNA靶基因,从而直接刺激该基因的翻译过程。Lin28对于PGCs的发育分化至关重要,其表达在小鼠PGCs发育过程中具有时空限制性,还可通过正、负双向途径调节PGC池内生殖细胞数。LIN28的异常表达可能是恶性GCTs发生的早期信号。Lin28还可能是Oct3/4和Nanog途径的上游调控因子,高度调控精原细胞、胚胎癌细胞的分化状态和正常生殖细胞的发育过程;Lin28B基因与青春期女童乳腺发育、男童变声和阴毛发育以及青春期生长高峰密切相关。
As a key member of the heterochronic gene family, Lin28 and its homolog Lin28B play an important regulatory role in the development of primordial germ cells (PGCs), the progression of germ cell tumors (GCTs), and sexual maturation effect. Not only does Lin28 bind to the precursor terminal loops of the let-7 miRNA family, it blocks the let-7 miRNA maturation process and induces let-7 precursor uridylation and degradation. At the same time, Lin28 also selectively binds to the mRNA target gene, thereby directly stimulating the translation process of the gene. Lin28 is crucial for the development and differentiation of PGCs. The expression of Lin28 has the limitation of space-time in the development of mouse PGCs, and can regulate the number of germ cells in the PGC pool through positive and negative bidirectional ways. Aberrant expression of LIN28 may be an early sign of malignant GCTs. Lin28 may also be upstream regulators of the Oct3 / 4 and Nanog pathways, highly regulating the differentiation status of spermatogonia and embryonic carcinoma cells and the development of normal germ cells; Lin28B gene is associated with breast development in adolescent girls, vocal change and pubic hair development in boys, Adolescent growth is closely related to the peak.