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27 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LIN28A
lin-28 RNA binding posttranscriptional regulator A
Chromosome 1 · 1p36.11
NCBI Gene: 79727Ensembl: ENSG00000131914.11HGNC: HGNC:15986UniProt: Q9H9Z2
186PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA 3'-end processingprotein bindingnucleuscytosolneurodegenerative diseaselysosomal storage diseasetype 2 diabetes mellitusbreast cancer
✦AI Summary

LIN28A is an RNA-binding protein that regulates developmental timing, pluripotency, and metabolism through two primary mechanisms. First, it suppresses let-7 microRNA biogenesis by binding pre-miRNA terminal loops containing a 5'-GGAG-3' motif and recruiting TUT4/TUT7 uridylyltransferases, causing uridylation and degradation of precursor miRNAs 1. Second, it functions as a translational enhancer, driving specific mRNAs including IGF2 and metabolic enzymes to polysomes and increasing protein synthesis efficiency 2. LIN28A is essential for skeletal muscle differentiation through IGF2 upregulation and maintains pluripotency in embryonic stem cells by preventing let-7-mediated differentiation 3. Clinically, LIN28A is aberrantly upregulated in multiple human cancers, contributing to cancer stem cell generation, epithelial-mesenchymal transition, and metabolic reprogramming 4. The LIN28A/let-7 regulatory loop promotes cellular proliferation, drug resistance, metastasis, and angiogenesis 5. The LIN28A rs34787247 G>A polymorphism increases cancer susceptibility in the Chinese population 6. Notably, LIN28A is a specific marker of pluripotent stem cell-derived extracellular vesicles, supporting their clinical translation for degenerative diseases 7. Emerging therapeutic strategies employ miRNA-based PROTACs targeting LIN28A degradation to restore let-7 expression and enhance chemotherapy sensitivity in breast cancer 8.

Sources cited
1
LIN28A recruits TUT4/TUT7 uridylyltransferases to uridylate pre-miRNAs, preventing Dicer processing and leading to degradation
PMID: 22118463
2
LIN28A inhibits let-7 processing and regulates translation of mRNAs controlling developmental timing, pluripotency, and metabolism
PMID: 21247876
3
LIN28 is one of four factors sufficient to reprogram human somatic cells to pluripotent stem cells alongside OCT4, SOX2, and NANOG
PMID: 18029452
4
LIN28A and LIN28B play roles in cancer stem cell properties, epithelial-mesenchymal transition, and metabolic reprogramming
PMID: 39152528
5
The LIN28A/LIN28B and let-7 loop is aberrantly regulated in cancers and contributes to cellular proliferation, drug resistance, metastasis, and other hallmarks of cancer
PMID: 26123544
6
LIN28A rs34787247 G>A polymorphism is associated with cancer susceptibility in the Chinese population
PMID: 39154245
7
LIN28A is specifically enriched in pluripotent stem cell-derived small extracellular vesicles and serves as a marker for their identification
PMID: 38321535
8
miRNA-based PROTACs targeting LIN28A degrade the protein and restore let-7 expression, inhibiting cancer cell proliferation and increasing chemotherapy sensitivity
PMID: 39292784
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.57Moderate
lysosomal storage diseaseOpen Targets
0.35Weak
type 2 diabetes mellitusOpen Targets
0.14Weak
breast cancerOpen Targets
0.11Weak
neoplasmOpen Targets
0.11Weak
cancerOpen Targets
0.10Suggestive
colorectal carcinomaOpen Targets
0.10Suggestive
acute myeloid leukemiaOpen Targets
0.09Suggestive
azoospermiaOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
Wilms tumorOpen Targets
0.08Suggestive
psoriasisOpen Targets
0.08Suggestive
papillary thyroid carcinomaOpen Targets
0.08Suggestive
gliomaOpen Targets
0.07Suggestive
triple-negative breast cancerOpen Targets
0.07Suggestive
spermatogenic failure 12Open Targets
0.07Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
spermatogenic failure 1Open Targets
0.06Suggestive
spermatogenic failure 48Open Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NANOGProtein interaction100%L1TD1Protein interaction99%CRIPTOProtein interaction98%KLF4Protein interaction98%DROSHAProtein interaction98%DPPA4Protein interaction98%
Tissue Expression6 tissues
Brain
100%
Ovary
33%
Liver
26%
Lung
19%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
LIN28ANANOGL1TD1CRIPTOKLF4DROSHADPPA4
PROTEIN STRUCTURE
Preparing viewer…
PDB5UDZ · 2.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.83LoF Tolerant
pLIⓘ
0.04Tolerant
Observed/Expected LoF0.50 [0.32–0.83]
RankingsWhere LIN28A stands among ~20K protein-coding genes
  • #2,307of 20,598
    Most Researched186 · top quartile
  • #7,092of 17,882
    Most Constrained (LOEUF)0.83
Genes detectedLIN28A
Sources retrieved27 papers
Response time—
📄 Sources
27▼
1
Induced pluripotent stem cell lines derived from human somatic cells.
PMID: 18029452
Science · 2007
1.00
2
Development of miRNA-based PROTACs targeting Lin28 for breast cancer therapy.
PMID: 39292784
Sci Adv · 2024
0.90
3
RNA-PROTACs: Degraders of RNA-Binding Proteins.
PMID: 33108679
Angew Chem Int Ed Engl · 2021
0.80
4
Microbiota-reprogrammed phosphatidylcholine inactivates cytotoxic CD8 T cells through UFMylation via exosomal SerpinB9 in multiple myeloma.
PMID: 40128181
Nat Commun · 2025
0.76
5
The association between LIN28A gene rare variants and Parkinson's disease in Chinese population.
PMID: 35447238
Gene · 2022
0.72