Download Gene Section LIN28B (lin-28 homolog B (C. elegans)) in Oncology and Haematology

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in Oncology and Haematology
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Gene Section
Mini Review
LIN28B (lin-28 homolog B (C. elegans))
Yung-Ming Jeng
Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University,
Taipei, Taiwan (YMJ)
Published in Atlas Database: July 2011
Online updated version : http://AtlasGeneticsOncology.org/Genes/LIN28BID45723ch6q16.html
DOI: 10.4267/2042/47262
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Function
Identity
It inhibits biosynthesis of let-7 microRNA through
promoting terminal uridylation of let-7 precusor by
TUTase4.
Other names: CSDD2, FLJ16517, Lin28.2
HGNC (Hugo): LIN28B
Location: 6q16.3
Note
Size: 146,72 kb. Orientation: plus strand.
Homology
Lin28
Mutations
DNA/RNA
Note
No somatic mutation of Lin28B was identified in
cancer.
Description
The gene spans over 125 kb on plus strand; 4 exons.
Transcription
Implicated in
The gene is mainly expressed in fetal tissues and not
expressed in adult tissue and reexpressed in cancer
tissue.
Hepatocellular carcinoma
Note
Lin28B expression is more frequently noted in highgrade hepatocellular carcinoma with high alphafetoprotein 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 epithelialmesenchymal transition in HA22T cells and hence,
invasion capacity.
Protein
Description
Lin28B is an oncofetal RNA-binding protein. Lin-28B
protein consists of two domains that contain RNAbinding 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.
Colorectal cancer
Note
Lin28B is overexpressed in colorectal cancer. It
promotes cell migration, invasion and transforms
Expression
Cytoplasm.
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(1)
20
LIN28B (lin-28 homolog B (C. elegans))
Jeng YM
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.
He C, Kraft P, Chen C, Buring JE, Paré G, Hankinson SE,
Chanock SJ, Ridker PM, Hunter DJ, Chasman DI. Genomewide association studies identify loci associated with age at
menarche and age at natural menopause. Nat Genet. 2009
Jun;41(6):724-8
Ovarian cancer
Lu L, Katsaros D, Shaverdashvili K, Qian B, Wu Y, de la
Longrais IA, Preti M, Menato G, Yu H. Pluripotent 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. Eur J Cancer. 2009 Aug;45(12):2212-8
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.
Viswanathan SR, Powers JT, Einhorn W, Hoshida Y, Ng TL,
Toffanin S, O'Sullivan M, Lu J, Phillips LA, Lockhart VL, Shah
SP, Tanwar PS, Mermel CH, Beroukhim R, Azam M, Teixeira
J, Meyerson M, Hughes TP, Llovet JM, Radich J, Mullighan
CG, Golub TR, Sorensen PH, Daley GQ. Lin28 promotes
transformation and is associated with advanced human
malignancies. Nat Genet. 2009 Jul;41(7):843-8
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.
Helland Å, Anglesio MS, George J, Cowin PA, Johnstone CN,
House CM, Sheppard KE, Etemadmoghadam D, Melnyk N,
Rustgi AK, Phillips WA, Johnsen H, Holm R, Kristensen GB,
Birrer MJ, Pearson RB, Børresen-Dale AL, Huntsman DG,
deFazio A, Creighton CJ, Smyth GK, Bowtell DD. Deregulation
of MYCN, LIN28B and LET7 in a molecular subtype of
aggressive high-grade serous ovarian cancers. PLoS One.
2011 Apr 13;6(4):e18064
King CE, Cuatrecasas M, Castells A, Sepulveda AR, Lee JS,
Rustgi AK. LIN28B promotes colon cancer progression and
metastasis. Cancer Res. 2011 Jun 15;71(12):4260-8
Body height
Note
A LIN28B SNP, rs314277, is associated with final
body height.
King CE, Wang L, Winograd R, Madison BB, Mongroo PS,
Johnstone CN, Rustgi AK. LIN28B fosters colon cancer
migration, invasion and transformation through let-7-dependent
and -independent mechanisms. Oncogene. 2011 Oct
6;30(40):4185-93
References
This article should be referenced as such:
Heo I, Joo C, Cho J, Ha M, Han J, Kim VN. Lin28 mediates the
terminal uridylation of let-7 precursor MicroRNA. Mol Cell.
2008 Oct 24;32(2):276-84
Jeng YM. LIN28B (lin-28 homolog B (C. elegans)). Atlas Genet
Cytogenet Oncol Haematol. 2012; 16(1):20-21.
Viswanathan SR, Daley GQ, Gregory RI. Selective blockade of
microRNA processing by Lin28. Science. 2008 Apr
4;320(5872):97-100
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(1)
21