Abstract
hsa-mir-483 is located within intron 2 of the IGF2 gene. We have previously shown oncogenic features of miR-483-3p through cooperation with IGF2 or by independently targeting the proapoptotic gene BBC3/PUMA. Here we demonstrate that expression of miR-483 can be induced independently of IGF2 by the oncoprotein β-catenin through an interaction with the basic helix-loop-helix protein upstream stimulatory transcription factor 1. We also show that β-catenin itself is a target of miR-483-3p, triggering a negative regulatory loop that becomes ineffective in cells harboring an activating mutation of β-catenin. These results provide insights into the complex regulation of the IGF2/miR-483 locus, revealing players in the β-catenin pathway.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Apoptosis Regulatory Proteins / genetics
-
Apoptosis Regulatory Proteins / metabolism
-
Cell Line, Tumor
-
Genetic Loci / genetics
-
HEK293 Cells
-
Humans
-
Insulin-Like Growth Factor II / genetics
-
Insulin-Like Growth Factor II / metabolism
-
Introns / genetics
-
MicroRNAs / genetics
-
MicroRNAs / metabolism*
-
Mutation*
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / metabolism
-
Transcription Factors / genetics
-
Transcription Factors / metabolism
-
beta Catenin / biosynthesis*
-
beta Catenin / genetics
Substances
-
Apoptosis Regulatory Proteins
-
BBC3 protein, human
-
IGF2 protein, human
-
MIRN483 microRNA, human
-
MicroRNAs
-
Proto-Oncogene Proteins
-
Transcription Factors
-
beta Catenin
-
Insulin-Like Growth Factor II