Author:
Li Lin,Li Qi,Zou Zhengrong,Huang Zoufang,Chen Yijian
Abstract
Background: Accumulating evidence suggests that members of the tripartite motif (TRIMs) family play a crucial role in the development and progression of hematological malignancy. Here, we explored the expression and potential role of TRIM10 in acute myeloid leukemia (AML). Methods: The expression levels of TRIM10 were investigated in AML patients and cell lines by RNA-seq, qRT-PCR and Western blotting analysis. Lentiviral infection was used to regulate the level of TRIM10 in AML cells. The effects of TRIM10 on apoptosis, drug sensitivity and proliferation of AML cells were evaluated by flow cytometry and cell-counting kit-8 (CCK-8) assay, as well as being assessed in a murine model. Results: TRIM10 mRNA and protein expression was reduced in primary AML samples and AML cell lines in comparison to the normal controls and a human normal hematopoietic cell line, respectively. Moreover, overexpression of TRIM10 in HL60 and K562 cells inhibited AML cell proliferation and induced cell apoptosis. The nude mice study further confirmed that overexpression of TRIM10 blocked tumor growth and inhibited cell proliferation. In contrast, knockdown of TRIM10 in AML cells showed contrary results. Subsequent mechanistic studies demonstrated that knockdown of TRIM10 enhanced the expression of nuclear protein P65, which implied the activation of the NF-κB signal pathway. Consistently, overexpression of TRIM10 in AML cells showed a contrary result. These data indicated that inactivation of the NF-κB pathway is involved in TRIM10-mediated regulation in AML. TRIM10 expression can be de-repressed by a combination that targets both DNA methyltransferase and histone deacetylase. Conclusions: Our results strongly suggested that TRIM10 plays a tumor suppressive role in AML development associated with the NF-κB signal pathway and may be a potential target of epigenetic therapy against leukemia.
Funder
the Doctoral Initiation Foundation of Gannan Medical University
the Horizontal topics Foundation of Gannan Medical University
the Key Laboratory of the Ministry of Education Foundation
Cited by
1 articles.
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