Curcumin attenuates Adriamycin-resistance of acute myeloid leukemia by inhibiting the lncRNA HOTAIR/miR-20a-5p/WT1 axis

• Published in: Laboratory investigation 2021-10, Vol.101 (10), p.1308-1317
• Main Authors: Liu, Jun-Min, Li, Min, Luo, Wei, Sun, Hong-Bo
• Format: Article
• Language: English
• Subjects: 64/60; 692/699; 692/699/1541; Acute myeloid leukemia; Antisense RNA; Antisense therapy; Apoptosis; Assaying; Bax protein; Cell cycle; Cell Line, Tumor; Cell migration; Cell proliferation; Cell Survival - drug effects; Cell viability; Chemotherapy; Curcumin; Curcumin - pharmacology; Doxorubicin - pharmacology; Drug resistance; Drug Resistance, Neoplasm - drug effects; Flow cytometry; Gene expression; HL-60 Cells; Humans; Laboratory Medicine; Leukemia; Leukemia, Myeloid, Acute - metabolism; Medicine; Medicine & Public Health; MicroRNAs - metabolism; miRNA; Myeloid leukemia; Pathology; Ribonucleic acid; RNA; RNA, Long Noncoding - metabolism; Signal Transduction - drug effects; Transcription; Western blotting; WT1 Proteins - metabolism
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/s41374-021-00640-3

Acute myeloid leukemia (AML) is a common subtype of leukemia, and a large proportion of patients with AML eventually develop drug resistance. Curcumin exerts cancer suppressive effects and increases sensitivity to chemotherapy in several diseases. This study aimed to investigate the mechanism by which curcumin affects the resistance of AML to Adriamycin by regulating HOX transcript antisense RNA (HOTAIR) expression. Cell viability, colony-formation, flow cytometry, and Transwell assays were used to assess cell proliferation, apoptosis, and migration. A dual-luciferase reporter assay was used to verify the interaction between microRNA (miR)-20a-5p and HOTAIR or Wilms' tumor 1 (WT1). RT-qPCR and Western blotting assays were performed to detect gene and protein expression. The results showed that curcumin suppressed the resistance to Adriamycin, inhibited the expression of HOTAIR and WT1, and promoted the expression of miR-20a-5p in human acute leukemia cells (HL-60) or Adriamycin-resistant HL-60 cells (HL-60/ADR). Furthermore, curcumin suppressed proliferation and promoted apoptosis of HL-60/ADR cells. Overexpression of HOTAIR reversed the regulatory effect of curcumin on apoptosis and migration and restored the effect of curcumin on inducing the expression of cleaved caspase3, Bax, and P27. In addition, HOTAIR upregulated WT1 expression by targeting miR-20a-5p, and inhibition of miR-20a-5p reversed the regulation of Adriamycin resistance by curcumin in AML cells. Finally, curcumin inhibited Adriamycin resistance by suppressing the HOTAIR/miR-20a-5p/WT1 pathway in vivo. In short, curcumin suppressed the proliferation and migration, blocked the cell cycle progression of AML cells, and sensitized AML cells to Adriamycin by regulating the HOTAIR/miR-20a-5p/WT1 axis. These findings suggest a potential role of curcumin and HOTAIR in AML treatment. The authors show that curcumin suppresses the proliferation and migration of acute myeloid leukemia (AML) cells. Curcumin also blocks cell cycle progression and sensitizes AML cells to Adriamycin by regulating the HOTAIR/miR-20a-5p/WT1 axis. These findings suggest a potential role of curcumin and HOTAIR in AML treatment.