Dihydroartemisinin-regulated mRNAs and lncRNAs in chronic myeloid leukemia

Oncotarget. 2017 Dec 15;9(2):2543-2552. doi: 10.18632/oncotarget.23274. eCollection 2018 Jan 5.

Abstract

Chronic myelocytic leukemia (CML) is characterized by increased and unregulated growth of predominantly myeloid cells in the bone marrow, and accumulation of these cells in blood. We investigated the effects of an anti-malarial drug, dihydroartemisinin (DHA), on K562 CML cells. We identified 34 mRNAs and eight lncRNAs dysregulated following DHA treatment in pure and hemin-induced K562 cells. Up- or downregulation of these potential DHA targets increased with increasing DHA concentration. We also constructed and analyzed a DHA-related mRNA-lncRNA regulation network in K562 cells, and found that four DHA-modulated mRNAs regulated by four lncRNAs participated in the steroid biosynthesis pathway. Some estrogen-related drugs, such as tamoxifen, shared common targets with DHA. We inferred that DHA exerted anti-cancer effects on K562 cells by influencing estrogen levels. Our findings indicate that DHA has potential not only as an anti-malarial drug, but also as an anti-CML chemotherapeutic.

Keywords: chronic myeloid leukemia; dihydroartemisinin; lncRNA-mRNA network; long non-coding RNA; steroid biosynthesis.