Ectopic over-expression of tristetraprolin in human cancer cells promotes biogenesis of let-7 by down-regulation of Lin28

Chae Won Kim; Mai-Tram Vo; Hong Kyeung Kim; Hyun Hee Lee; Nal Ae Yoon; Byung Ju Lee; Young Joo Min; Won Duk Joo; Hee Jeong Cha; Jeong Woo Park; Wha Ja Cho

doi:10.1093/nar/gkr1302

Ectopic over-expression of tristetraprolin in human cancer cells promotes biogenesis of let-7 by down-regulation of Lin28

Nucleic Acids Res. 2012 May;40(9):3856-69. doi: 10.1093/nar/gkr1302. Epub 2011 Dec 30.

Authors

Chae Won Kim¹, Mai-Tram Vo, Hong Kyeung Kim, Hyun Hee Lee, Nal Ae Yoon, Byung Ju Lee, Young Joo Min, Won Duk Joo, Hee Jeong Cha, Jeong Woo Park, Wha Ja Cho

Affiliation

¹ Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.

Abstract

Tristetraprolin (TTP) is a AU-rich element (ARE) binding protein and exhibits suppressive effects on cell growth through down-regulation of ARE-containing oncogenes. The let-7 microRNA has emerged as a significant factor in tumor suppression. Both TTP and let-7 are often repressed in human cancers, thereby promoting oncogenesis by derepressing their target genes. In this work, an unexpected link between TTP and let-7 has been found in human cancer cells. TTP promotes an increase in expression of mature let-7, which leads to the inhibition of let-7 target gene CDC34 expression and suppresses cell growth. This event is associated with TTP-mediated inhibition of Lin28, which has emerged as a negative modulator of let-7. Lin28 mRNA contains ARE within its 3'-UTR and TTP enhances the decay of Lin28 mRNA through binding to its 3'-UTR. This suggests that the TTP-mediated down-regulation of Lin28 plays a key role in let-7 miRNA biogenesis in cancer cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions
Adenocarcinoma / genetics
Adenocarcinoma / metabolism
Anaphase-Promoting Complex-Cyclosome
Cell Growth Processes
Cell Line, Tumor
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Down-Regulation*
Female
Gene Expression Regulation, Neoplastic*
Humans
MicroRNAs / biosynthesis*
Neoplasms / genetics
Neoplasms / metabolism
Neoplasms / pathology
Ovarian Neoplasms / genetics
Ovarian Neoplasms / metabolism
RNA Stability
RNA, Messenger / metabolism
RNA-Binding Proteins
Tristetraprolin / metabolism*
Ubiquitin-Conjugating Enzymes
Ubiquitin-Protein Ligase Complexes / genetics
Ubiquitin-Protein Ligase Complexes / metabolism

Substances

3' Untranslated Regions
DNA-Binding Proteins
LIN28B protein, human
MicroRNAs
RNA, Messenger
RNA-Binding Proteins
Tristetraprolin
mirnlet7 microRNA, human
CDC34 protein, human
Ubiquitin-Conjugating Enzymes
Ubiquitin-Protein Ligase Complexes
Anaphase-Promoting Complex-Cyclosome