title: Lin28: primal regulator of growth and metabolism in stem cells.
abstract: In recent years, the highly conserved Lin28 RNA-binding proteins have emerged as factors that define stemness in several tissue lineages. Lin28 proteins repress let-7 microRNAs and influence mRNA translation, thereby regulating the self-renewal of mammalian embryonic stem cells. Subsequent discoveries revealed that Lin28a and Lin28b are also important in organismal growth and metabolism, tissue development, somatic reprogramming, and cancer. In this review, we discuss the Lin28 pathway and its regulation, outline its roles in stem cells, tissue development, and pathogenesis, and examine the ramifications for re-engineering mammalian physiology.
authors.affiliation: Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Ng
authors.initials: N
authors.lastname: Shyh-Chang
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D047108:Embryonic Development / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D016601:RNA-Binding Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D016601:RNA-Binding Proteins
references.citation: Gerontology. 2012;58(4):337-43
references.pmid: 22261798
references.citation: Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18283-8
references.pmid: 21990348
references.citation: Dev Biol. 1981 Feb;82(1):41-55
references.pmid: 7014288
references.citation: Nat Genet. 2009 Jul;41(7):843-8
references.pmid: 19483683
references.citation: Trends Cell Biol. 2008 Oct;18(10):505-16
references.pmid: 18774294
references.citation: Cell. 2012 Sep 14;150(6):1209-22
references.pmid: 22980981
references.citation: Genes Dev. 2006 Aug 15;20(16):2202-7
references.pmid: 16882971
references.citation: Cell. 2011 Nov 23;147(5):1080-91
references.pmid: 22078496
references.citation: Genes Dev. 2007 May 1;21(9):1125-38
references.pmid: 17473174
references.citation: Nature. 2008 Dec 4;456(7222):593-8
references.pmid: 19052619
references.citation: Cell Stem Cell. 2010 May 7;6(5):468-78
references.pmid: 20452321
references.citation: Science. 2008 Apr 4;320(5872):97-100
references.pmid: 18292307
references.citation: Mod Pathol. 2011 Feb;24(2):288-96
references.pmid: 21057460
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5014-9
references.pmid: 17360327
references.citation: Cell Metab. 2011 Aug 3;14(2):264-71
references.pmid: 21803296
references.citation: Cell. 2007 Dec 14;131(6):1109-23
references.pmid: 18083101
references.citation: Science. 2012 Mar 9;335(6073):1195-200
references.pmid: 22345399
references.citation: J Neurooncol. 2012 Jan;106(1):71-9
references.pmid: 21725800
references.citation: Cell Stem Cell. 2010 Sep 3;7(3):279-82
references.pmid: 20804964
references.citation: Nat Genet. 2012 Oct;44(10):1126-30
references.pmid: 22941191
references.citation: Cell Death Differ. 2012 Mar;19(3):378-86
references.pmid: 21979467
references.citation: Genes Dev. 2010 Mar 1;24(5):478-90
references.pmid: 20194440
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3384-9
references.pmid: 19211792
references.citation: Cell. 2012 Nov 9;151(4):765-777
references.pmid: 23102813
references.citation: RNA Biol. 2007 Jan-Mar;4(1):16-25
references.pmid: 17617744
references.citation: Cell. 2010 Dec 23;143(7):1059-71
references.pmid: 21145579
references.citation: Nat Cell Biol. 2010 Nov;12(11):1101-7
references.pmid: 20935637
references.citation: Curr Biol. 2002 Apr 30;12(9):735-9
references.pmid: 12007417
references.citation: Nature. 2000 Feb 24;403(6772):901-6
references.pmid: 10706289
references.citation: Cell Metab. 2011 Oct 5;14(4):443-51
references.pmid: 21982705
references.citation: Mol Cell. 2012 Oct 26;48(2):195-206
references.pmid: 22959275
references.citation: Science. 2007 Mar 16;315(5818):1576-9
references.pmid: 17322030
references.citation: EMBO J. 2011 Dec 14;30(24):4851-2
references.pmid: 22166995
references.citation: Dev Biol. 2003 Jun 15;258(2):432-42
references.pmid: 12798299
references.citation: Science. 2012 May 25;336(6084):1040-4
references.pmid: 22628656
references.citation: Nat Cell Biol. 2008 Aug;10(8):987-93
references.pmid: 18604195
references.citation: Nature. 2010 Mar 25;464(7288):520-8
references.pmid: 20336134
references.citation: Cell Stem Cell. 2012 Oct 5;11(4):491-504
references.pmid: 23040478
references.citation: Development. 2001 Jun;128(12):2333-9
references.pmid: 11493552
references.citation: Cell. 2009 Nov 13;139(4):693-706
references.pmid: 19878981
references.citation: Cell Cycle. 2009 Mar 15;8(6):843-52
references.pmid: 19221491
references.citation: Genes Dev. 2009 Apr 1;23(7):862-76
references.pmid: 19293287
references.citation: Cell Stem Cell. 2009 Jun 5;4(6):487-92
references.pmid: 19497275
references.citation: Epigenetics. 2012 Sep;7(9):1079-90
references.pmid: 22894909
references.citation: Development. 2010 Mar;137(6):891-900
references.pmid: 20179095
references.citation: Cell Stem Cell. 2012 Dec 7;11(6):769-82
references.pmid: 23217423
references.citation: PLoS Genet. 2012;8(3):e1002588
references.pmid: 22457637
references.citation: Int J Androl. 2011 Aug;34(4 Pt 2):e160-74
references.pmid: 21631526
references.citation: Cancer Res. 2011 Jun 15;71(12):4260-8
references.pmid: 21512136
references.citation: Cell. 2011 Nov 23;147(5):1066-79
references.pmid: 22118463
references.citation: Genes Dev. 2000 Jun 15;14(12):1512-27
references.pmid: 10859169
references.citation: Nat Chem Biol. 2010 Jun;6(6):411-7
references.pmid: 20436487
references.citation: EMBO J. 2011 Nov 15;30(24):4860-73
references.pmid: 22085932
references.citation: RNA. 2008 Aug;14(8):1539-49
references.pmid: 18566191
references.citation: Cell. 2005 Mar 11;120(5):635-47
references.pmid: 15766527
references.citation: Development. 2010 Oct;137(19):3185-92
references.pmid: 20823062
references.citation: Cell. 1997 Mar 7;88(5):637-46
references.pmid: 9054503
references.citation: Hum Pathol. 2011 May;42(5):710-8
references.pmid: 21288558
references.citation: J Biol Chem. 2012 May 18;287(21):17386-17397
references.pmid: 22467868
references.citation: Nature. 2000 Nov 2;408(6808):86-9
references.pmid: 11081512
references.citation: Histopathology. 2011 Sep;59(3):452-9
references.pmid: 22034885
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18668-73
references.pmid: 19828440
references.citation: Nature. 2012 Mar 04;483(7391):598-602
references.pmid: 22388813
references.citation: Science. 2009 Apr 3;324(5923):95-8
references.pmid: 19342589
references.citation: Genes Cells. 1999 Oct;4(10):563-72
references.pmid: 10583505
references.citation: Dev Biol. 2003 Jul 15;259(2):364-79
references.pmid: 12871707
references.citation: BMC Dev Biol. 2009 Jun 29;9:38
references.pmid: 19563657
references.citation: Genes Dev. 2008 Jun 15;22(12):1591-6
references.pmid: 18559475
references.citation: Cell. 2011 Sep 30;147(1):81-94
references.pmid: 21962509
references.citation: Science. 2009 Jun 26;324(5935):1670-3
references.pmid: 19556499
references.citation: Cell. 2012 Oct 26;151(3):521-32
references.pmid: 23063654
references.citation: PLoS Genet. 2011 Sep;7(9):e1002242
references.pmid: 21935352
references.citation: Dev Cell. 2005 Sep;9(3):403-14
references.pmid: 16139228
references.citation: Nat Genet. 2012 Nov;44(11):1199-206
references.pmid: 23042116
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21558-63
references.pmid: 21118985
references.citation: Nat Commun. 2012 Jun 26;3:923
references.pmid: 22735451
references.citation: Cancer Res. 2006 Dec 15;66(24):11613-22
references.pmid: 17178855
references.citation: Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15828-33
references.pmid: 21896756
references.citation: Science. 2009 May 22;324(5930):1029-33
references.pmid: 19460998
references.citation: Genetics. 1980 Oct;96(2):435-54
references.pmid: 7262539
references.citation: Nucleic Acids Res. 2009 Aug;37(14):4850-61
references.pmid: 19528081
references.citation: Nat Genet. 2011 Jul 31;43(9):869-74
references.pmid: 21804546
references.citation: Nature. 2009 Dec 3;462(7273):595-601
references.pmid: 19898493
references.citation: Exp Gerontol. 2003 Jan-Feb;38(1-2):137-43
references.pmid: 12543271
references.citation: Cancer Cell. 2012 Oct 16;22(4):524-35
references.pmid: 23079661
references.citation: Nat Cell Biol. 2009 Feb;11(2):197-203
references.pmid: 19136965
references.citation: Blood. 2012 Nov 1;120(18):3764-73
references.pmid: 22976955
references.citation: Nature. 2010 Jul 1;466(7302):133-7
references.pmid: 20596026
references.citation: Stem Cells. 2011 Mar;29(3):496-504
references.pmid: 21425412
references.citation: Cold Spring Harb Symp Quant Biol. 2011;76:369-74
references.pmid: 21960526
references.citation: Mol Cell. 2008 Oct 24;32(2):276-84
references.pmid: 18951094
references.citation: JAMA. 2011 Mar 2;305(9):903-12
references.pmid: 21364139
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21505-10
references.pmid: 21118986
references.citation: Science. 2013 Jan 11;339(6116):222-6
references.pmid: 23118012
references.citation: Cell. 2008 Oct 17;135(2):227-39
references.pmid: 18957199
references.citation: Nature. 2010 Feb 4;463(7281):621-6
references.pmid: 20054295
references.citation: Cell Stem Cell. 2010 Dec 3;7(6):651-5
references.pmid: 21112560
references.citation: Cancer Cell. 2010 Nov 16;18(5):510-23
references.pmid: 21075313
references.citation: Cancer Res. 2007 Aug 15;67(16):7713-22
references.pmid: 17699775
references.citation: FASEB J. 2007 Feb;21(2):415-26
references.pmid: 17167072
references.citation: Nature. 2010 Jul 29;466(7306):637-41
references.pmid: 20671708
references.citation: Cell Stem Cell. 2010 Feb 5;6(2):167-74
references.pmid: 20096661
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14235-40
references.pmid: 20660734
references.citation: RNA. 2013 May;19(5):613-26
references.pmid: 23481595
references.citation: Development. 2013 Jun;140(12):2535-47
references.pmid: 23715547
references.citation: Cell. 2009 Aug 21;138(4):696-708
references.pmid: 19703396
references.citation: Gene. 2006 Dec 15;384:51-61
references.pmid: 16971064
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14229-34
references.pmid: 20616003
references.citation: Gene Expr Patterns. 2003 Dec;3(6):719-26
references.pmid: 14643679
references.citation: Cell. 1997 Oct 3;91(1):25-34
references.pmid: 9335332
references.citation: Mol Cell Biol. 2009 Oct;29(19):5290-305
references.pmid: 19635812
references.citation: Nat Genet. 2010 Jul;42(7):626-30
references.pmid: 20512147
references.citation: Development. 1998 Apr;125(7):1191-205
references.pmid: 9477318
references.citation: Cancer Res. 2007 Oct 15;67(20):9762-70
references.pmid: 17942906
references.citation: Genes Dev. 2012 Sep 1;26(17):1926-44
references.pmid: 22899010
references.citation: Science. 1984 Oct 26;226(4673):409-16
references.pmid: 6494891
references.citation: Science. 2009 Jul 24;325(5939):435-9
references.pmid: 19589965
references.citation: Lancet Oncol. 2012 Aug;13(8):838-48
references.pmid: 22691720
references.citation: Development. 2012 Dec;139(24):4514-23
references.pmid: 23172912
references.citation: Genes Dev. 2007 May 1;21(9):1025-30
references.pmid: 17437991
references.citation: RNA. 2012 Oct;18(10):1875-85
references.pmid: 22898984
references.citation: Stem Cells. 2013 May;31(5):1001-9
references.pmid: 23378032
references.citation: Nat Struct Mol Biol. 2011 Mar;18(3):302-8
references.pmid: 21297634
references.citation: Nature. 2002 Jan 3;415(6867):45-53
references.pmid: 11780111
references.citation: PLoS One. 2011;6(6):e20820
references.pmid: 21695257
references.citation: Curr Biol. 2010 Feb 9;20(3):271-7
references.pmid: 20116247
references.citation: Cell Stem Cell. 2011 Mar 4;8(3):294-308
references.pmid: 21362569
references.citation: Cell. 1981 Apr;24(1):59-69
references.pmid: 7237544
references.citation: Proc Natl Acad Sci U S A. 2004 May 25;101(21):8034-8
references.pmid: 15148368
references.citation: Cancer Res. 2008 Apr 15;68(8):2587-91
references.pmid: 18413726
references.citation: Blood. 2012 Aug 2;120(5):1048-59
references.pmid: 22723554
references.citation: Nat Cell Biol. 2012 Feb 26;14(3):266-75
references.pmid: 22366686
references.citation: J Cell Biol. 2011 Jan 10;192(1):69-81
references.pmid: 21200031
references.citation: Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4233-8
references.pmid: 22366319
references.citation: Genes Dev. 2003 Dec 15;17(24):3011-6
references.pmid: 14681208
references.citation: Nature. 2009 Aug 13;460(7257):909-13
references.pmid: 19578360
references.citation: RNA. 2009 Mar;15(3):357-61
references.pmid: 19147696
references.citation: Nature. 2006 May 25;441(7092):475-82
references.pmid: 16598206
references.citation: Cell. 1999 Mar 5;96(5):701-12
references.pmid: 10089885
references.citation: J Biol Chem. 2011 May 6;286(18):16121-30
references.pmid: 21378162
references.citation: Nature. 2011 Aug 18;476(7360):346-50
references.pmid: 21760589
references.citation: EMBO J. 2006 Dec 13;25(24):5794-804
references.pmid: 17139256
references.citation: J Exp Med. 2008 Oct 27;205(11):2499-506
references.pmid: 18936236
references.citation: Cell. 2008 Aug 8;134(3):521-33
references.pmid: 18692474
references.citation: Nat Genet. 1998 Jun;19(2):182-6
references.pmid: 9620778
references.citation: Nat Struct Mol Biol. 2009 Oct;16(10):1016-20
references.pmid: 19713957
references.citation: J Biol Chem. 2009 Mar 13;284(11):6605-9
references.pmid: 19126550
references.citation: Nucleic Acids Res. 2011 May;39(9):3724-34
references.pmid: 21247876
references.citation: Science. 2007 Dec 21;318(5858):1917-20
references.pmid: 18029452
references.citation: Cell. 2012 Jan 20;148(1-2):259-72
references.pmid: 22225612
references.citation: Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21075-80
references.pmid: 22160727
references.citation: Nat Struct Mol Biol. 2009 Oct;16(10):1021-5
references.pmid: 19713958
references.citation: Development. 2012 May;139(10):1788-97
references.pmid: 22510985
references.citation: PLoS One. 2010 Nov 12;5(11):e15486
references.pmid: 21103394