Curcumin Attenuates Adriamycin-resistance of Acute Myeloid Leukemia by Inhibiting the LncRNA HOTAIR/miR-20a-5p/WT1 Axis

Overview

Journal Lab Invest

Specialty Pathology

Date 2021 Jul 20

PMID 34282279

Citations 18

Authors

Jun-Min Liu

Min Li

Wei Luo

Hong-Bo Sun

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Macrophages in graft-versus-host disease (GVHD): dual roles as therapeutic tools and targets.

Raoufi A, Soleimani Samarkhazan H, Nouri S, Khaksari M, Abbasi Sourki P, Sargazi Aval O Clin Exp Med. 2025; 25(1):73.

PMID: 40048037 PMC: 11885342. DOI: 10.1007/s10238-025-01588-0.

Research Progress on Natural Products That Regulate miRNAs in the Treatment of Osteosarcoma.

Wang L, Liu X, Lv H, Zhang H, Lin R, Xu S Biology (Basel). 2025; 14(1).

PMID: 39857292 PMC: 11759184. DOI: 10.3390/biology14010061.

Multifaceted functions of the Wilms tumor 1 protein: From its expression in various malignancies to targeted therapy.

Nian Q, Lin Y, Zeng J, Zhang Y, Liu R Transl Oncol. 2024; 52():102237.

PMID: 39672002 PMC: 11700300. DOI: 10.1016/j.tranon.2024.102237.

The role of curcumin in modulating circular RNAs and long non-coding RNAs in cancer.

Rismanchi H, Malek Mohammadi M, Mafi A, Khalilzadeh P, Farahani N, Mirzaei S Clin Transl Oncol. 2024; .

PMID: 39623194 DOI: 10.1007/s12094-024-03782-0.

Expression of and as potential biomarkers in chronic myeloid leukemia patients in Brazil.

Kubaski Benevides A, Marin A, Wosniaki D, Oliveira R, Koerich G, Kusma B Front Oncol. 2024; 14:1443346.

PMID: 39450252 PMC: 11499243. DOI: 10.3389/fonc.2024.1443346.

References

Shang J, Chen W, Liu S, Wang Z, Wei T, Chen Z . CircPAN3 contributes to drug resistance in acute myeloid leukemia through regulation of autophagy. Leuk Res. 2019; 85:106198. DOI: 10.1016/j.leukres.2019.106198. View

Bertoli S, Picard M, Berard E, Griessinger E, Larrue C, Mouchel P . Dexamethasone in hyperleukocytic acute myeloid leukemia. Haematologica. 2018; 103(6):988-998. PMC: 6058767. DOI: 10.3324/haematol.2017.184267. View

Dohner H, Weisdorf D, Bloomfield C . Acute Myeloid Leukemia. N Engl J Med. 2015; 373(12):1136-52. DOI: 10.1056/NEJMra1406184. View

Deck L, Hunsaker L, Vander Jagt T, Whalen L, Royer R, Vander Jagt D . Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin. Eur J Med Chem. 2017; 143:854-865. DOI: 10.1016/j.ejmech.2017.11.048. View

Deguchi A . Curcumin targets in inflammation and cancer. Endocr Metab Immune Disord Drug Targets. 2015; 15(2):88-96. DOI: 10.2174/1871530315666150316120458. View

Moradi-Marjaneh R, Hassanian S, Rahmani F, Aghaee-Bakhtiari S, Avan A, Khazaei M . Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer. Curr Pharm Des. 2019; 24(39):4626-4638. DOI: 10.2174/1381612825666190110145151. View

Ramezani M, Hatamipour M, Sahebkar A . Promising anti-tumor properties of bisdemethoxycurcumin: A naturally occurring curcumin analogue. J Cell Physiol. 2017; 233(2):880-887. DOI: 10.1002/jcp.25795. View

Zhou S, Li J, Xu H, Zhang S, Chen X, Chen W . Liposomal curcumin alters chemosensitivity of breast cancer cells to Adriamycin via regulating microRNA expression. Gene. 2017; 622:1-12. DOI: 10.1016/j.gene.2017.04.026. View

Kouhpeikar H, Butler A, Bamian F, Barreto G, Majeed M, Sahebkar A . Curcumin as a therapeutic agent in leukemia. J Cell Physiol. 2019; 234(8):12404-12414. DOI: 10.1002/jcp.28072. View

10.

Pimentel-Gutierrez H, Bobadilla-Morales L, Barba-Barba C, Ortega-de-la-Torre C, Sanchez-Zubieta F, Corona-Rivera J . Curcumin potentiates the effect of chemotherapy against acute lymphoblastic leukemia cells via downregulation of NF-κB. Oncol Lett. 2016; 12(5):4117-4124. PMC: 5104245. DOI: 10.3892/ol.2016.5217. View

11.

Cheetham S, Gruhl F, Mattick J, Dinger M . Long noncoding RNAs and the genetics of cancer. Br J Cancer. 2013; 108(12):2419-25. PMC: 3694235. DOI: 10.1038/bjc.2013.233. View

12.

Mercer T, Dinger M, Mattick J . Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009; 10(3):155-9. DOI: 10.1038/nrg2521. View

13.

Feng Y, Shen Y, Chen H, Wang X, Zhang R, Peng Y . Expression profile analysis of long non-coding RNA in acute myeloid leukemia by microarray and bioinformatics. Cancer Sci. 2017; 109(2):340-353. PMC: 5797823. DOI: 10.1111/cas.13465. View

14.

Mozdarani H, Ezzatizadeh V, Rahbar Parvaneh R . The emerging role of the long non-coding RNA HOTAIR in breast cancer development and treatment. J Transl Med. 2020; 18(1):152. PMC: 7119166. DOI: 10.1186/s12967-020-02320-0. View

15.

Li N, Meng D, Gao L, Xu Y, Liu P, Tian Y . Overexpression of HOTAIR leads to radioresistance of human cervical cancer via promoting HIF-1α expression. Radiat Oncol. 2018; 13(1):210. PMC: 6201557. DOI: 10.1186/s13014-018-1153-4. View

16.

Wang H, Qin R, Guan A, Yao Y, Huang Y, Jia H . HOTAIR enhanced paclitaxel and doxorubicin resistance in gastric cancer cells partly through inhibiting miR-217 expression. J Cell Biochem. 2018; 119(9):7226-7234. DOI: 10.1002/jcb.26901. View

17.

Hao S, Shao Z . HOTAIR is upregulated in acute myeloid leukemia and that indicates a poor prognosis. Int J Clin Exp Pathol. 2015; 8(6):7223-8. PMC: 4525952. View

18.

Guo L, Zhu Y, Li L, Zhou S, Yin G, Yu G . Breast cancer cell-derived exosomal miR-20a-5p promotes the proliferation and differentiation of osteoclasts by targeting SRCIN1. Cancer Med. 2019; 8(12):5687-5701. PMC: 6745844. DOI: 10.1002/cam4.2454. View

19.

Zhao F, Pu Y, Qian L, Zang C, Tao Z, Gao J . MiR-20a-5p promotes radio-resistance by targeting NPAS2 in nasopharyngeal cancer cells. Oncotarget. 2017; 8(62):105873-105881. PMC: 5739686. DOI: 10.18632/oncotarget.22411. View

20.

Ping L, Jian-Jun C, Chu-Shu L, Guang-Hua L, Ming Z . Silencing of circ_0009910 inhibits acute myeloid leukemia cell growth through increasing miR-20a-5p. Blood Cells Mol Dis. 2019; 75:41-47. DOI: 10.1016/j.bcmd.2018.12.006. View