Imbalanced expression of polycistronic miRNA in acute myeloid leukemia

• Published in: International journal of hematology 2017-12, Vol.106 (6), p.811-819
• Main Authors: Kotaki, Ryutaro, Higuchi, Hiroshi, Ogiya, Daisuke, Katahira, Yasuhiro, Kurosaki, Natsumi, Yukihira, Naoko, Ogata, Jun, Yamamoto, Haruna, Mohamad Alba, Syakira, Azhim, Azran, Kitajima, Tatsuo, Inoue, Shigeaki, Morishita, Kazuhiro, Ono, Koh, Koyama-Nasu, Ryo, Kotani, Ai
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Deregulation; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Gene expression; Gene Expression Regulation, Leukemic; Gene therapy; Hematology; HL-60 Cells; Humans; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; MDS1 and EVI1 Complex Locus Protein - biosynthesis; MDS1 and EVI1 Complex Locus Protein - genetics; Medicine; Medicine & Public Health; MicroRNAs - biosynthesis; MicroRNAs - genetics; miRNA; Multigene Family; Myeloid leukemia; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Oncology; Original Article; Post-transcription; Ribonucleic acid; RNA; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; RNA-binding protein; THP-1 Cells; Transcription; U937 Cells; Viruses
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-017-2314-1

miR-1 and miR-133 are clustered on the same chromosomal loci and are transcribed together as a single transcript that is positively regulated by ecotropic virus integration site-1 (EVI1). Previously, we described how miR-133 has anti-tumorigenic potential through repression of EVI1 expression. It has also been reported that miR-1 is oncogenic in the case of acute myeloid leukemia (AML). Here, we show that expression of miR-1 and miR-133, which have distinct functions, is differentially regulated between AML cell lines. Interestingly, the expression of miR-1 and EVI1, which binds to the promoter of the miR-1/miR-133 cluster, is correlative. The expression levels of TDP-43, an RNA-binding protein that has been reported to increase the expression, but inhibits the activity, of miR-1, were not correlated with expression levels of miR-1 in AML cells. Taken together, our observations raise the possibility that the balance of polycistronic miRNAs is regulated post-transcriptionally in a hierarchical manner possibly involving EVI1, suggesting that the deregulation of this balance may play some role in AML cells with high EVI1 expression.