Abstract
Lin-28 and lin-28B are RNA-binding proteins which can block microRNA let-7 maturation
and affect the differentiation and proliferation of embryonic stem cells. Lin-28 may
also regulate the expression of insulin-like growth factor II (IGF-II). As one of
the pluripotent factors involved in making induced pluripotent stem cells (iPS), lin-28 is considered a potential therapeutic target for cancer treatment. To further understand
the role of lin-28 in cancer, we analysed the expression of lin-28 and its homologue lin-28B in tumour samples, and evaluated their associations with let-7a maturation, IGF-II expression,
disease features and outcomes in 211 patients with primary epithelial ovarian cancer.
The analysis showed that both lin-28 and lin-28B were positively correlated with primary and pre-let-7a-3; lin-28B, not lin-28, was inversely correlated with mature let-7a. A positive correlation was also observed
between lin-28B and IGF-II expression, while no association was found between lin-28B and IGF-I or IGFBP-3. The study further demonstrated that lin-28B expression was associated with the risk of disease progression and death; patients
with high lin-28B had shorter progression-free and overall survival than those with low lin-28B. These results seem to support the findings of recent in vitro experiments, showing that lin-28 blocks the process of let-7a maturation. Our study
also suggests that lin-28B may promote ovarian cancer progression and serve as an
unfavourable prognostic marker for the disease. The correlation between lin-28B and IGF-II indicates that the growth factor may mediate the effect of lin-28B on
tumour growth.
Keywords
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References
- The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans.Nature. 2000; 403: 901-906
- The let-7 microRNA represses cell proliferation pathways in human cells.Cancer Res. 2007; 67: 7713-7722
- Widespread changes in protein synthesis induced by microRNAs.Nature. 2008; 455: 58-63
- Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation.Science. 2007; 315: 1576-1579
- Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2.Cell Cycle. 2007; 6: 2585-2590
- Let-7 regulates self renewal and tumorigenicity of breast cancer cells.Cell. 2007; 131: 1109-1123
- Let-7 microRNA functions as a potential growth suppressor in human colon cancer cells.Biol Pharm Bull. 2006; 29: 903-906
- Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival.Cancer Res. 2004; 64: 3753-3756
- Let-7 expression defines two differentiation stages of cancer.Proc Natl Acad Sci USA. 2007; 104: 11400-11405
- Suppression of non-small cell lung tumor development by the let-7 microRNA family.Proc Natl Acad Sci USA. 2008; 105: 3903-3908
- The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function.Cancer Res. 2007; 67: 1419-1423
- Selective blockade of microRNA processing by Lin28.Science. 2008; 320: 97-100
- Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing.RNA. 2008; 14: 1539-1549
- Determinants of microRNA processing inhibition by the developmentally regulated RNA-binding protein Lin28.J Biol Chem. 2008; 283: 21310-21314
- Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-II expression and favorable prognosis.Cancer Res. 2007; 67: 10117-10122
- Induced pluripotent stem cell lines derived from human somatic cells.Science. 2007; 318: 1917-1920
- The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA.Cell. 1997; 88: 637-646
- Temporally regulated expression of lin-28 in diverse tissues of the developing mouse.Gene Exp Patterns. 2003; 3: 719-726
- Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma.Gene. 2006; 384: 51-61
- Lin-28 binds IGF-2 mRNA and participates in skeletal myogenesis by increasing translation efficiency.Genes Dev. 2007; 21: 1125-1138
- The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer.Clin Cancer Res. 2006; 12: 1208-1214
- Promoter-specific transcription of insulin-like growth factor-II in epithelial ovarian cancer.Gynecol Oncol. 2006; 103: 990-995
- Insulin-like growth factors control cell migration in health and disease.Int J Biochem Cell Biol. 2007; 39: 890-909
- Glutathione S-transferase polymorphisms and ovarian cancer treatment and survival.Gynecol Oncol. 2006; 100: 330-337
- IGF-I in epithelial ovarian cancer and its role in disease progression.Growth Factors. 2007; 25: 346-354
Gee HE, Camps C, Buffa FM, et al. MicroRNA-10b and breast cancer metastasis. Nature 2008;455:E8–9 [author reply E9].
- Methylation of the insulin-like growth factor binding protein-3 gene and prognosis of epithelial ovarian cancer.Int J Gynecol Cancer. 2006; 16: 210-218
- Lin28 mediates the terminal uridylation of let-7 precursor microRNA.Mol Cell. 2008; 32: 276-284
- A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment.Nat Cell Biol. 2008; 10: 987-993
- Switching from repression to activation: microRNAs can up-regulate translation.Science. 2007; 318: 1931-1934
- A hierarchical network controls protein translation during murine embryonic stem cell self-renewal and differentiation.Cell Stem Cell. 2008; 2: 448-460
- Localization of the developmental timing regulator Lin28 to mRNP complexes, P-bodies and stress granules.RNA Biol. 2007; 4: 16-25
- Regulation of signaling genes by TGFbeta during entry into dauer diapause in C. elegans.BMC Dev Biol. 2004; 4: 11
- Impaired microRNA processing enhances cellular transformation and tumorigenesis.Nat Genet. 2007; 39: 673-677
- Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferation.Proc Natl Acad Sci USA. 2009; 106: 3384-3389
Article info
Publication history
Published online: May 28, 2009
Accepted:
May 1,
2009
Received in revised form:
April 28,
2009
Received:
March 4,
2009
Identification
Copyright
© 2009 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
