LIN28B (lin-28 homolog B (C. elegans))

2011-07-01   Yung-Ming Jeng 

Department of Biochemistry, Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan

Identity

HGNC
LOCATION
6q16.3
LOCUSID
ALIAS
CSDD2
FUSION GENES

DNA/RNA

Description

The gene spans over 125 kb on plus strand; 4 exons.

Transcription

The gene is mainly expressed in fetal tissues and not expressed in adult tissue and reexpressed in cancer tissue.

Proteins

Description

Lin28B is an oncofetal RNA-binding protein. Lin-28B protein consists of two domains that contain RNA-binding motif: the N-terminal cold shock domain and a pair of retroviral-type CCHC zinc fingers. It inhibits biosynthesis of let-7 microRNA through binding to the 5-GGAG-3 motif in the terminal loop of pre-let-7 and promoting terminal uridylation of let-7 precusor by TUTase4. Uridylated pre-let-7 miRNAs fail to be processed by Dicer and undergo degradation.

Expression

Cytoplasm.

Function

It inhibits biosynthesis of let-7 microRNA through promoting terminal uridylation of let-7 precusor by TUTase4.

Homology

Lin28

Mutations

Note

No somatic mutation of Lin28B was identified in cancer.

Implicated in

Entity name
Hepatocellular carcinoma
Note
Lin28B expression is more frequently noted in high-grade hepatocellular carcinoma with high alpha-fetoprotein levels. Knockdown of Lin28B by RNA interference in the HCC cell line suppressed proliferation in vitro and reduced in vivo tumor growth in NOD/SCID mice. In contrast, overexpression of Lin28B in the HCC cell line enhanced tumorigenicity. Overexpression of Lin28B also induced epithelial-mesenchymal transition in HA22T cells and hence, invasion capacity.
Entity name
Colorectal cancer
Note
Lin28B is overexpressed in colorectal cancer. It promotes cell migration, invasion and transforms immortalized colonic epithelial cells. In addition, constitutive LIN28B expression increases expression of intestinal stem cell markers LGR5 and PROM1 in the presence of let-7 restoration.
Entity name
Ovarian cancer
Note
Lin28B is overexpressed in high grade serous ovarian cancer. Pleomorphism in Lin28B promoter region is associated with susceptibility to epithelium ovarian cancer. Patients with high Lin28B ovarian cancer had shorter progression-free and overall survival than those with low Lin28B ovarian cancer.
Entity name
Age at menarche
Note
A sequence variation in Lin28B is identified as the SNP most significant associated with age at menarche in one genome wide study. Besides, a meta-analysis of 32 genome-wide association studies in 87802 women found polymorphism of Lin28B is strongly associated with age at menarche. Knockout mice of Lin28B also show delay in puberty onset.
Entity name
Body height
Note
A LIN28B SNP, rs314277, is associated with final body height.

Bibliography

Pubmed IDLast YearTitleAuthors
194486212009Genome-wide association studies identify loci associated with age at menarche and age at natural menopause.He C et al
215332842011Deregulation of MYCN, LIN28B and LET7 in a molecular subtype of aggressive high-grade serous ovarian cancers.Helland Å et al
189510942008Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA.Heo I et al
215121362011LIN28B promotes colon cancer progression and metastasis.King CE et al
216252102011LIN28B fosters colon cancer migration, invasion and transformation through let-7-dependent and -independent mechanisms.King CE et al
194776332009Pluripotent factor lin-28 and its homologue lin-28b in epithelial ovarian cancer and their associations with disease outcomes and expression of let-7a and IGF-II.Lu L et al
194836832009Lin28 promotes transformation and is associated with advanced human malignancies.Viswanathan SR et al

Other Information

Locus ID:

NCBI: 389421
MIM: 611044
HGNC: 32207
Ensembl: ENSG00000187772

Variants:

dbSNP: 389421
ClinVar: 389421
TCGA: ENSG00000187772
COSMIC: LIN28B

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000187772ENST00000345080Q6ZN17
ENSG00000187772ENST00000635857A0A1B0GTK2
ENSG00000187772ENST00000637759A0A1B0GVD3

Expression (GTEx)

0
1
2
3
4
5

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
194836832009Lin28 promotes transformation and is associated with advanced human malignancies.341
221184632011Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms.246
192117922009Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferation.175
194486212009Genome-wide association studies identify loci associated with age at menarche and age at natural menopause.142
230421162012LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression.135
229411912012Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma.122
271809062016SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b.79
273200422016LIN28 Regulates Stem Cell Metabolism and Conversion to Primed Pluripotency.73
215332842011Deregulation of MYCN, LIN28B and LET7 in a molecular subtype of aggressive high-grade serous ovarian cancers.71
229769552012Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B.61

Citation

Yung-Ming Jeng

LIN28B (lin-28 homolog B (C. elegans))

Atlas Genet Cytogenet Oncol Haematol. 2011-07-01

Online version: http://atlasgeneticsoncology.org/gene/45723/lin28b-(lin-28-homolog-b-(c-elegans))