Loss of let-7 binding sites resulting from truncations of the 3' untranslated region of HMGA2 mRNA in uterine leiomyomas

Abstract

A subset of uterine leiomyomas (UL) shows chromosomal rearrangements of the region 12q14 approximately q15, leading to an overexpression of the high-mobility group protein A2 gene (HMGA2). Recent studies identified microRNAs of the let-7 family as post-transcriptional regulators of HMGA2. Intragenic chromosomal breakpoints might cause truncated HMGA2 transcripts lacking part of the 3' UTR. The corresponding loss of let-7 complementary sites (LCS) located in the 3' UTR would therefore stabilize HMGA2 mRNA. The aim of this study was to check UL with rearrangements of the chromosomal region 12q14 approximately 15 for truncated HMGA2 transcripts by real-time reverse-transcription polymerase chain reaction. In 8/13 leiomyomas with aberrations of chromosomal region 12q15, the results showed the presence of the complete 3' UTR with all LCS. A differential expression with highly reduced 3' untranslated region levels was found in 5/13 myomas. In two of these, full-length transcripts were almost undetectable. Truncated transcripts were apparently predominant in roughly one-third of UL with chromosomal rearrangements affecting the HMGA2 locus, where they lead to a higher stability of its transcripts and subsequently contribute to the overexpression of the protein. The assay used is also generally suited to detect submicroscopic alterations leading to truncated transcripts of HMGA2.