LIN28A Gene - RNA-Binding Protein Regulating Development and Cancer
Comprehensive genomic and functional analysis of LIN28A, a key regulator of stem cell pluripotency and oncogenesis
Gene Information Card
| Symbol | LIN28A |
|---|---|
| Full Name | lin-28 homolog A |
| Gene Type | protein-coding |
| Chromosomal Location | 1p36.11 |
| NCBI Gene ID | 79727 ncbi.nlm.nih.gov/gene/79727 |
| Ensembl ID | ENSG00000131914 |
| UniProt ID | Q9H9Z2 |
| OMIM ID | 611043 |
| HGNC ID | 15986 |
| Aliases | LIN28, ZCCHC1, CSDD1 |
Description
LIN28A encodes a conserved RNA-binding protein that plays a critical role in development, stem cell pluripotency, and metabolism. It binds to the let-7 family of microRNAs and blocks their maturation, thereby promoting self-renewal and proliferation. LIN28A is frequently overexpressed in various cancers and is associated with poor prognosis. It also interacts with mRNAs involved in cell growth and differentiation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | LIN28A overexpression suppresses let-7 microRNA biogenesis, leading to de-repression of oncogenes such as MYC and RAS. | COSMIC, ClinVar |
| Primordial Dwarfism (rare) | Germline missense mutations in LIN28A disrupt RNA-binding and let-7 regulation, impairing growth. | OMIM #611043, ClinVar |
| Type 2 Diabetes (associated) | LIN28A variants influence insulin sensitivity and glucose metabolism via let-7 targets. | NCBI Gene, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Placenta | 8.2 | Medium |
| Brain (cerebellum) | 4.1 | Low |
| Liver | 1.3 | Low |
| Heart | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| H1 (embryonic stem cell) | 15.0 | High expression; consistent with stem cell role |
| HeLa (cervical carcinoma) | 9.5 | Overexpressed |
| MCF7 (breast cancer) | 7.2 | Overexpressed |
| K562 (leukemia) | 3.1 | Moderate |
| HEK293 (embryonic kidney) | 2.0 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.200G>A (p.Arg67His) | Missense | <0.1% | Reduced RNA-binding affinity; associated with primordial dwarfism |
| c.337C>T (p.Arg113Trp) | Missense | <0.1% | Impaired let-7 repression; linked to growth disorders |
| Amplification | Copy number gain | 5-10% in cancers | Increased LIN28A expression; promotes tumorigenesis |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg67His, p.Arg113Trp) reduce RNA-binding and let-7 inhibition, leading to developmental growth defects.
Gain of Function (GOF)
Gene amplification or overexpression in cancers enhances let-7 suppression, driving oncogene activation and proliferation.
Dominant Negative (DN)
Not reported for LIN28A.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • mRNA 3'-UTR binding (GO:0003730) |
| • pre-miRNA binding (GO:0070878) | • regulation of gene silencing by miRNA (GO:0060968) |
| • positive regulation of cell population proliferation (GO:0008284) | • negative regulation of miRNA maturation (GO:1903799) |
Pathways
• let-7 inhibition of oncogenes (MYC
• RAS
• HMGA2)
• Pluripotency and self-renewal (OCT4
• NANOG
• SOX2)
• Insulin/IGF signaling and glucose metabolism
Protein Summary
LIN28A is a 209-amino acid RNA-binding protein containing a cold-shock domain (CSD) and two CCHC zinc finger motifs. It binds to the terminal loop of let-7 precursor microRNAs and recruits the TUTase ZCCHC11 to add oligo(U) tails, blocking Dicer processing and promoting degradation. LIN28A also interacts with mRNAs encoding ribosomal proteins and metabolic enzymes. Its expression is high in embryonic stem cells and many cancers, where it maintains an undifferentiated, proliferative state.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LIN28A Knockout HEK293 Cell Line | EDJ-KQ14079 | Human | 79727 | Details Get a Quote |
| LIN28A Knockout HeLa Cell Line | EDJ-KQ57212 | Human | 79727 | Details Get a Quote |
| LIN28A Knockout A-549 Cell Line | EDJ-KQ65727 | Human | 79727 | Details Get a Quote |
| LIN28A Knockout HCT 116 Cell Line | EDJ-KQ74144 | Human | 79727 | Details Get a Quote |
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