Neurosurgery notes/Tumours/Tumour genetics/LIN28A

LIN28A

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Parent item
Tumour genetics

Gene loci

  • Chromosome 1p24.3.

Normal function

  • RNA-binding protein
    • Regulating
      • Let-7 miRNA biogenesis
      • Translation of IGF2
      • Metabolic enzymes
    • Promotes stem cell self-renewal
    • Differentiation block
  • Mechanism
    • LIN28A binds to the terminal loop structure of pre-let-7 microRNA precursors.
    • It recruits terminal uridylyltransferases TUT4 (ZCCHC11) or TUT7 (ZCCHC6), which add multiple uridine nucleotides (oligo-uridylation) to the 3' end of pre-let-7.
    • The uridyne tail prevents recognition and cleavage by the Dicer enzyme, blocking maturation into functional let-7 miRNA and leading to its degradation.
  • Cytoplasmically located but can be transported to nucleus

Mutation effects

  • Rare mutations
  • Overexpression of LIN28A represses let-7 → Enhances translation of oncogenic mRNAs (HMGA2, Cyclin), promotes proliferation, EMT, stemness.

Clinical association

  • Overexpressed
    • Embryogenic tumour with multilayered rosettes
      • Diagnostic marker for embryogenic tumour with multilayered rosettes
    • Germ cell tumours
    • Glioblastoma
    • ATRT
    • Poor prognosis biomarker