LIN28B Human

LIN28B was initially discovered as a homolog of the C. elegans gene lin-28, which is part of the heterochronic pathway that regulates the timing of developmental events . In various organisms, including mice, humans, Xenopus, zebrafish, and Drosophila, LIN28B is expressed early during development and in undifferentiated tissues . Its expression is downregulated as development and cellular differentiation proceed .

LIN28B is best known for its role in promoting pluripotency by regulating the microRNA let-7 . It functions as a gatekeeper molecule that regulates the transition between pluripotency and committed cell lineages, both in let-7-dependent and let-7-independent manners . LIN28B is highly expressed in embryonic stem cells and is downregulated in response to differentiation . It has been identified as one of several factors that can participate in the reprogramming of mammalian somatic cells to pluripotent cells .

LIN28B selectively blocks the expression of let-7 microRNA family members, which act as tumor suppressors by inhibiting the expression of oncogenes and key regulators of mitogenic pathways, including RAS, MYC, and HMGA2 . LIN28B represses let-7 maturation through a TUTase-independent mechanism . This regulation is crucial for maintaining the balance between self-renewal and differentiation in stem cells and for promoting transformation and tumor progression in cancer cells .

Overexpression of LIN28B is associated with poor prognosis in various cancers, such as oral squamous cell carcinoma, colon cancer, epithelial ovarian carcinoma, gastric cancer, hepatocellular carcinoma, breast cancer, and esophagus cancer . It functions as an oncogene by promoting transformation and tumor progression . Given its significant prognostic value, LIN28B is considered a promising biomarker for cancer prognosis .