Details

Autor(en) / Beteiligte

• Oyejobi, Greater Kayode
• Yan, Xiaodan
• Sliz, Piotr
• Wang, Longfei

Titel

Regulating Protein-RNA Interactions: Advances in Targeting the LIN28/Let-7 Pathway

Ist Teil von

• International journal of molecular sciences, 2024-04, Vol.25 (7), p.3585

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2024

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Originally discovered in , LIN28 is an evolutionarily conserved zinc finger RNA-binding protein (RBP) that post-transcriptionally regulates genes involved in developmental timing, stem cell programming, and oncogenesis. LIN28 acts via two distinct mechanisms. It blocks the biogenesis of the lethal-7 (let-7) microRNA (miRNA) family, and also directly binds messenger RNA (mRNA) targets, such as IGF-2 mRNA, and alters downstream splicing and translation events. This review focuses on the molecular mechanism of LIN28 repression of let-7 and current strategies to overcome this blockade for the purpose of cancer therapy. We highlight the value of the LIN28/let-7 pathway as a drug target, as multiple oncogenic proteins that the pathway regulates are considered undruggable due to their inaccessible cellular location and lack of cavities for small molecule binding.