Protein lin-28 homolog B (LIN28B)

Lin28 homolog B (LIN28B) is a highly conserved RNA-binding protein that serves as a master regulator of developmental timing and pluripotency [3, 13]. It primarily functions by inhibiting the biogenesis of the let-7 family of microRNAs, which are potent tumor suppressors that promote cellular differentiation [1, 4]. By sequestering primary let-7 transcripts in the nucleolus or recruiting uridyltransferases for their degradation, LIN28B prevents the maturation of let-7, leading to the derepression of oncogenic targets such as MYC, RAS, and HMGA2 [1, 2, 15]. While its expression is largely restricted to embryonic development and specific adult tissues like the placenta and testis, LIN28B is frequently reactivated in a wide range of human malignancies, including neuroblastoma, hepatocellular carcinoma, and lung cancer [1, 5, 6]. This reactivation promotes cancer stemness, epithelial-to-mesenchymal transition, and metastasis, making it a significant biomarker for poor clinical outcomes [1, 12, 17]. Current therapeutic efforts are focused on developing small-molecule inhibitors that disrupt the interaction between LIN28B and let-7 to restore tumor-suppressive miRNA activity [9, 16]. However, targeting LIN28B remains challenging due to the shallow and dynamic nature of its RNA-binding domains [7].

Other names

CSDD2Lin-28.2lin-28BLin-28 homolog B

Inhibition of the LIN28B-let-7 interaction to restore tumor-suppressive let-7 microRNA levels and suppress downstream oncogenic targets [1, 9, 15].