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J Cancer 2023; 14(1):99-113. doi:10.7150/jca.54775 This issue Cite

Research Paper

Loss of MiR-155 Sensitizes FLT3-ITD+AML to Chemotherapy and FLT3 Inhibitors via Glycolysis Blocking by Targeting PIK3R1

Lingyan Wang#, Peifang Jiang#, Jiazheng Li#, Yan Huang, Jingjing Wen, Zhengjun Wu, Yanxin Chen, Jianda Hu✉

Fujian Medical University Union Hospital, Fujian Provincial Key Laboratory on Hematology, Fujian Institute of Hematology, Fuzhou 350001
# These authors contributed equally to this work.

✉ Corresponding author: Jianda Hu drjiandahucom

Citation:
Wang L, Jiang P, Li J, Huang Y, Wen J, Wu Z, Chen Y, Hu J. Loss of MiR-155 Sensitizes FLT3-ITD+AML to Chemotherapy and FLT3 Inhibitors via Glycolysis Blocking by Targeting PIK3R1. J Cancer 2023; 14(1):99-113. doi:10.7150/jca.54775. https://www.jcancer.org/v14p0099.htm
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Abstract

Graphic abstract

FLT3 tyrosine kinase inhibitors in combination with chemotherapy have shown some success in patients with FLT3 mutations. But a variety of mechanisms have led to the rapid resistance to the treatment. One of the most prominent is the metabolic alteration on aerobic glycolysis. We aim to explore the role of a high expressing microRNA, miR-155, in mediating resistance to chemotherapy and FLT3 inhibitor treatment. The deep sequencing data mining revealed the connection between glycolysis and drug resistance. MV411 cells with miR-155 knockout (KO) not only had increased sensitivity to FLT3 inhibitors but also Adriamycin (ADM) treatment. When combined with glycolysis inhibition the treatment response in MV411 cells further increased. Whereas in miR-155 KO cells, a lower glucose consumption level and lactic acid level were observed, and western blotting showed a decreased expression of key enzymes in glycolysis pathways. A negative correlation between PIK3R1 and miR-155 level can be observed in the sequencing data from FLT3-ITD+ AML patients. Moreover, luciferase reporter assay revealed that the 3'UTR of PIK3R1 mRNA can interact with the seed sequence of miR-155-5p. In conclusion, the loss of miR-155 increased treatment sensitivity to both chemotherapy and FLT3 inhibitors in FLT3-ITD+ AML cells via glycolysis blocking by targeting PIK3R1.

Keywords: Aerobic Glycolysis, MiR-155, FLT3-ITD, Quizartinib (AC220), Drug Resistance

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APA
Wang, L., Jiang, P., Li, J., Huang, Y., Wen, J., Wu, Z., Chen, Y., Hu, J. (2023). Loss of MiR-155 Sensitizes FLT3-ITD+AML to Chemotherapy and FLT3 Inhibitors via Glycolysis Blocking by Targeting PIK3R1. Journal of Cancer, 14(1), 99-113. https://doi.org/10.7150/jca.54775.

ACS
Wang, L.; Jiang, P.; Li, J.; Huang, Y.; Wen, J.; Wu, Z.; Chen, Y.; Hu, J. Loss of MiR-155 Sensitizes FLT3-ITD+AML to Chemotherapy and FLT3 Inhibitors via Glycolysis Blocking by Targeting PIK3R1. J. Cancer 2023, 14 (1), 99-113. DOI: 10.7150/jca.54775.

NLM
Wang L, Jiang P, Li J, Huang Y, Wen J, Wu Z, Chen Y, Hu J. Loss of MiR-155 Sensitizes FLT3-ITD+AML to Chemotherapy and FLT3 Inhibitors via Glycolysis Blocking by Targeting PIK3R1. J Cancer 2023; 14(1):99-113. doi:10.7150/jca.54775. https://www.jcancer.org/v14p0099.htm

CSE
Wang L, Jiang P, Li J, Huang Y, Wen J, Wu Z, Chen Y, Hu J. 2023. Loss of MiR-155 Sensitizes FLT3-ITD+AML to Chemotherapy and FLT3 Inhibitors via Glycolysis Blocking by Targeting PIK3R1. J Cancer. 14(1):99-113.

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