Protein lin-28 homolog A (LIN28A)

Protein lin-28 homolog A (LIN28A) is an evolutionarily conserved RNA-binding protein that plays a major role in regulating developmental timing, maintaining stem cell pluripotency, and controlling cell proliferation[1][2]. LIN28A acts by binding selectively to guanine-rich (G-quadruplex) elements in miRNAs and mRNAs, notably inhibiting the processing of pre-let-7 microRNAs, thereby blocking the maturation of the tumor suppressor let-7 miRNA and enhancing the translation of mRNAs involved in growth, metabolism, and pluripotency[1][2][5]. LIN28A is highly expressed in embryonic stem cells but downregulated in differentiated tissue, except for skeletal and cardiac muscle; its overexpression is observed in various cancers and is associated with poor prognosis, increased proliferation, impaired differentiation, and altered metabolic regulation[2][5]. Drugs targeting LIN28A, such as G4-binding molecules (e.g., N-methyl mesoporphyrin IX), can potentially inhibit its function by disrupting its interaction with RNA substrates, affecting both stem cell properties and tumorigenic potential[1].

Other names

Lin-28 homolog ALIN28Lin28aZinc-finger protein LIN-28A

Inhibition of LIN28A disrupts its binding to G-quadruplex (G4) motifs in RNA, relieving its suppression of let-7 microRNA maturation and altering translation of associated mRNAs[1].