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

Sun,Hang; Li,Youjie; Wang,Xiao; Zhou,Xue; Rong,Simin; Liang,Dongmin; Sun,Guangbin; Cao,Huizhen; Sun,Hongfang; Wang,Ranran; Yan,Yunfei; Xie,Shuyang; Sun,Yunxiao

doi:10.3892/ijo.2022.5339

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

Authors:
- Hang Sun
- Youjie Li
- Xiao Wang
- Xue Zhou
- Simin Rong
- Dongmin Liang
- Guangbin Sun
- Huizhen Cao
- Hongfang Sun
- Ranran Wang
- Yunfei Yan
- Shuyang Xie
- Yunxiao Sun
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Affiliations: Department of Pediatrics, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China, Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong 264033, P.R. China, School of Rehabilitation Medicine, Binzhou Medical University, Yantai, Shandong 264033, P.R. China
Published online on: March 17, 2022 https://doi.org/10.3892/ijo.2022.5339
Article Number: 49
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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