Development of miRNA-based PROTACs targeting Lin28 for breast cancer therapy.

ABSTRACT: Lin28, a highly conserved carcinogenic protein, plays an important role in the generation of cancer stem cells, contributing to the unfavorable prognosis of cancer patients. This RNA binding protein specifically binds to pri/pre-microRNA (miRNA) lethal-7 (let-7), impeding its miRNA maturation. The reduced expression of tumor suppressor miRNA let-7 fosters development and progression-related traits such as proliferation, invasion, metastasis, and drug resistance. We report a series of miRNA-based Lin28A-miRNA proteolysis-targeting chimeras (Lin28A-miRNA-PROTACs) designed to efficiently degrade Lin28A through a ubiquitin-proteasome-dependent mechanism, resulting in up-regulation of mature let-7 family. The augmented levels of matured let-7 miRNAs further exert inhibitory effects on cancer ce

SUBMITTER: Xu J 

PROVIDER: S-EPMC11409961 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature