TRIB2 regulates the expression of miR-33a-5p through the ERK/c-Fos pathway to affect the imatinib resistance of chronic myeloid leukemia cells

Chronic myeloid leukemia (CML) is a hematological disease, and imatinib (IM) resistance represents a major problem for its clinical treatment. In the present study, the role of tribbles pseudokinase 2 (TRIB2) in IM resistance of CML and the possible mechanism were investigated. It was found that TRIB2 was highly expressed in IM-resistant patients with CML through the Oncomine database and this conclusion was confirmed using reverse transcription-quantitative PCR and western blot experiments. Knockdown of TRIB2 was found to increase the drug sensitivity of KG cells to IM using Cell-Counting Kit-8 (CCK-8) assays, and the low-expression TRIB2 mice were further found to be more sensitive to the IM and have a higher survival rate in leukemia model mice. Moreover, using western blot and luciferase experiments, it was found that TRIB2 could regulate c-Fos through the ERK signaling pathway, and c-Fos suppressed the transcriptional activity and the expression of miR-33a-5p. Further investigation identified that the binding site for c-Fos to function on miR-33a-5p was the -958-965 region. Finally, CCK-8 assays and western blot experiments demonstrated that miR-33a-5p could inhibit the proliferation of KG cells and reduce IM resistance by suppressing the expression of HMGA2. In conclusion, it was demonstrated that TRIB2 regulates miR-33a-5p to reverse IM resistance in CML, which may help identify novel targets and therapeutic strategies for the clinical treatment of IM resistance.

Automated summary

The study found that TRIB2 is highly expressed in IM-resistant patients with CML and has an effect on the expression of miR-33a-5p through the ERK signaling pathway. miR-33a-5p can inhibit the proliferation of KG cells and reduce IM resistance by suppressing the expression of HMGA2.