PMID- 21625210
OWN - NLM
STAT- MEDLINE
DCOM- 20111122
LR  - 20230603
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 30
IP  - 40
DP  - 2011 Oct 6
TI  - LIN28B fosters colon cancer migration, invasion and transformation through 
      let-7-dependent and -independent mechanisms.
PG  - 4185-93
LID - 10.1038/onc.2011.131 [doi]
AB  - Lin28b is an RNA-binding protein that inhibits biogenesis of let-7 microRNAs. 
      LIN28B is overexpressed in diverse cancers, yet a specific role in the molecular 
      pathogenesis of colon cancer has to be elucidated. We have determined that human 
      colon tumors exhibit decreased levels of mature let-7 isoforms and increased 
      expression of LIN28B. To determine LIN28B's mechanistic role in colon cancer, we 
      expressed LIN28B in immortalized colonic epithelial cells and human colon cancer 
      cell lines. We found that LIN28B 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. This may occur as a result of Lin28b protein 
      binding LGR5 and PROM1 mRNA, suggesting that a subset of LIN28B functions is 
      independent of its ability to repress let-7. Our findings establish a new role 
      for LIN28B in human colon cancer pathogenesis, and suggest LIN28B 
      post-transcriptionally regulates LGR5 and PROM1 through a let-7-independent 
      mechanism.
FAU - King, C E
AU  - King CE
AD  - Gastroenterology Division and Department of Medicine, University of Pennsylvania, 
      Philadelphia, PA 19104, USA.
FAU - Wang, L
AU  - Wang L
FAU - Winograd, R
AU  - Winograd R
FAU - Madison, B B
AU  - Madison BB
FAU - Mongroo, P S
AU  - Mongroo PS
FAU - Johnstone, C N
AU  - Johnstone CN
FAU - Rustgi, A K
AU  - Rustgi AK
LA  - eng
GR  - P30 DK050306/DK/NIDDK NIH HHS/United States
GR  - U24 DK085532/DK/NIDDK NIH HHS/United States
GR  - U01 DK085532/DK/NIDDK NIH HHS/United States
GR  - P30 CA016520/CA/NCI NIH HHS/United States
GR  - P30-DK050306/DK/NIDDK NIH HHS/United States
GR  - R01 DK056645-12/DK/NIDDK NIH HHS/United States
GR  - R01-DK056645/DK/NIDDK NIH HHS/United States
GR  - U01-DK085551/DK/NIDDK NIH HHS/United States
GR  - R01 DK056645/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110530
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (LIN28B protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (mirnlet7 microRNA, human)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Movement/*physiology
MH  - Colonic Neoplasms/*pathology
MH  - DNA-Binding Proteins/*physiology
MH  - Humans
MH  - MicroRNAs/*physiology
MH  - *Neoplasm Invasiveness
MH  - RNA-Binding Proteins
PMC - PMC3165068
MID - NIHMS282253
EDAT- 2011/06/01 06:00
MHDA- 2011/12/13 00:00
PMCR- 2012/04/06
CRDT- 2011/06/01 06:00
PHST- 2011/06/01 06:00 [entrez]
PHST- 2011/06/01 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2012/04/06 00:00 [pmc-release]
AID - onc2011131 [pii]
AID - 10.1038/onc.2011.131 [doi]
PST - ppublish
SO  - Oncogene. 2011 Oct 6;30(40):4185-93. doi: 10.1038/onc.2011.131. Epub 2011 May 30.