Targeting Lin28: Insights into Biology and Advances with AI-Driven Drug Development

Abstract

Lin28, a conserved RNA-binding protein, promotes cancer stem cell features, epithelial-to-mesenchymal transition, and treatment resistance. Lin28 regulates mRNA translation, RNA stability, and transcription, which improve tumor plasticity and treatment resistance, in addition to suppressing let-7 microRNA production. Lin28 is an interesting cancer target due to its many functions; however, its structural complexity makes treatment development difficult. Lin28's proven and new non-canonical activities in cancer biology are examined in this work, focusing on cancer stem cell maintenance, metastasis, and treatment resistance. We highlight computational drug discovery advances targeting Lin28 utilizing virtual screening and machine learning. Generative artificial intelligence has made it easier to develop inhibitors for challenging targets like Lin28. This work integrates current knowledge and technology to demonstrate Lin28's therapeutic potential and outline future techniques to overcome RNA-binding protein targeting challenges.