Document Detail


Polo-like kinase 1 regulates cell proliferation and is targeted by miR-593* in esophageal cancer.
MedLine Citation:
PMID:  21170987     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Polo-like kinase 1 (PLK1) is overexpressed in various human cancers. However, the biological functions and the post-transcriptional regulations of PLK1 in esophageal cancer (EC) are still unknown. The purposes of our study are to determine whether PLK1 can be a molecular target of EC therapy and to identify a microRNA (miRNA) targeting PLK1. We performed loss-of-function and gain-of-function experiments regarding cell proliferation, cell cycle, apoptosis, in vivo tumor formation and luciferase reporter assays, using siRNAs against PLK1 and miRNA. PLK1 protein was expressed in all 11 EC cell lines, but not in normal esophageal epithelial cells (HEEpiC). Knockdown of PLK1 in EC cells induced G2/M arrest (p < 0.001) in cell cycle assay and reduced cell proliferation (p = 0.019) and tumor formation ability in vivo (p < 0.0001). MiR-593*, identified as a miRNA targeting PLK1 by a database search, was less expressed especially in six EC cell lines than HEEpiC cells. Moreover, miR-593* expression level was inversely correlated with PLK1 mRNA level in 48 clinical tissue specimens of EC (p = 0.006). Introduction of synthetic miR-593* suppressed PLK1 expression by 69-73%, reduced cell proliferation (p = 0.008) and increased cell proportion of G2/M phase (p = 0.01) in HSA/c (an EC cells), whereas a miR-593* inhibitor upregulated PLK1 expression by 11-55%. Additionally, luciferase assay demonstrated that miR-593* interacted two binding sites in the PLK1 3'-UTR and reduced 56.8-71.5% of luciferase activity by degrading luciferase mRNA in HSA/c cells. In conclusion, PLK1 is post-transcriptionally regulated by miR-593* and could be a promising molecular target for EC treatment.
Authors:
Tetsuo Ito; Fumiaki Sato; Takatsugu Kan; Yulan Cheng; Stefan David; Rachana Agarwal; Bogdan C Paun; Zhe Jin; Alexandru V Olaru; James P Hamilton; Florin M Selaru; Jian Yang; Nobutoshi Matsumura; Kazuharu Shimizu; John M Abraham; Yutaka Shimada; Yuriko Mori; Stephen J Meltzer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-11
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  129     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2012-06-27     Completed Date:  2013-01-24     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2134-46     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 UICC.
Affiliation:
Division of Gastroenterology, Department of Medicine and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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MeSH Terms
Descriptor/Qualifier:
3' Untranslated Regions
Adult
Aged
Aged, 80 and over
Animals
Base Sequence
Cell Cycle Proteins / genetics*,  metabolism*
Cell Line, Tumor
Cell Proliferation
Esophageal Neoplasms / enzymology*,  genetics*
Gene Expression Regulation, Neoplastic
Gene Silencing
Humans
Male
Mice
Mice, Nude
MicroRNAs / metabolism*
Middle Aged
Protein-Serine-Threonine Kinases / genetics*,  metabolism*
Proto-Oncogene Proteins / genetics*,  metabolism*
RNA Stability
RNA, Messenger / metabolism
Grant Support
ID/Acronym/Agency:
CA01808-01/CA/NCI NIH HHS; CA106763/CA/NCI NIH HHS; CA85069/CA/NCI NIH HHS; DK064388/DK/NIDDK NIH HHS; R01 CA001808/CA/NCI NIH HHS; R01 CA001808-05/CA/NCI NIH HHS; R01 CA146799/CA/NCI NIH HHS; R01 CA146799-03/CA/NCI NIH HHS; U01 CA085069/CA/NCI NIH HHS; U01 CA085069-10S2/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/3' Untranslated Regions; 0/Cell Cycle Proteins; 0/MIRN593 microRNA, human; 0/MicroRNAs; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/polo-like kinase 1
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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