MiR-92a-1-5p contributes to cellular proliferation and survival in chronic myeloid leukemia and its inhibition...

Area of Science:

• Hematology
• Molecular Biology
• Oncology

Background:

• Tyrosine kinase inhibitors (TKIs) like imatinib have transformed chronic myeloid leukemia (CML) therapy.
• TKI resistance and intolerance necessitate novel therapeutic strategies, such as targeting multiple oncogenic drivers.
• The miR-17-92 cluster is implicated in CML, but the specific role of miR-92a-1-5p requires elucidation.

Purpose of the Study:

• To investigate the role of miR-92a-1-5p in CML.
• To evaluate the therapeutic potential of combining miR-92a-1-5p inhibition with imatinib treatment.

Main Methods:

• Assessed miR-92a-1-5p expression in BCR::ABL1-positive myeloid cell lines and CML patient samples treated with imatinib.
• Performed gain- and loss-of-function studies for miR-92a-1-5p.
• Investigated the effects of miR-92a-1-5p inhibition on proliferation, cell death, and autophagy.
• Identified and validated BNIP3L (NIX) and TP53INP1 as target genes.

Main Results:

• Imatinib downregulates miR-92a-1-5p in BCR::ABL1-positive cells and CML samples.
• Inhibition of miR-92a-1-5p reduces proliferation and enhances imatinib-induced cell death.
• Overexpression of miR-92a-1-5p increases proliferation and reduces imatinib's effect on cell death.
• miR-92a-1-5p targets BNIP3L to regulate autophagy and TP53INP1 to control proliferation and cell cycle.

Conclusions:

• miR-92a-1-5p plays a role in CML progression.
• Inhibiting miR-92a-1-5p potentiates the anti-leukemic effects of imatinib.
• Combined inhibition of miR-92a-1-5p and imatinib represents a promising therapeutic strategy for CML.