Lin28b-flox Mouse

Lin28b, an RNA-binding protein, targets a wide range of microRNAs, modulating their maturation and activity. It is crucial in embryogenic stem cells under normal conditions, blocking differentiation and promoting proliferation. Lin28b can also influence the epithelial-to-mesenchymal transition by repressing let-7 microRNA biogenesis [5].

In breast cancer, Lin28b-high cells promote lung metastasis by building an immune-suppressive pre-metastatic niche. They enable neutrophil recruitment and N2 conversion, and breast cancer-released exosomes with low let-7s, mainly from Lin28b-induced breast cancer stem cells, are essential for this immune suppression [1]. In pancreas cancer, the Lin28b/Wnt5a axis drives the disease through crosstalk between cancer-associated fibroblasts and tumor epithelium [2]. In neuroendocrine prostate cancer, LIN28B transcription is up-regulated, and its depletion by CRISPR inhibits tumorigenesis and xenograft growth, with its functions mediated mainly through let-7 miRNA suppression [3]. In endometrial cancer, LIN28B binds and stabilizes PCAT5, which in turn stabilizes IGF2BP3, promoting aerobic glycolysis, proliferation, migration, and invasion of EC cells [4].

In conclusion, Lin28b plays essential roles in tumor progression and metastasis in multiple solid tumor entities. Model-based research, especially through gene knockout or conditional knockout mouse models, has revealed its significant contributions to breast, pancreas, prostate, and endometrial cancers, highlighting its potential as a therapeutic target and biomarker in these disease areas.