Abstract
Tripartite motif (TRIM) 31 is a member of TRIM family and exerts oncogenic role in the progression and drug resistance of several cancers. However, little is known about the relevance of TRIM31 in acute myeloid leukemia (AML). Herein, we investigated the role of TRIM31 in AML. We examined the expression levels of TRIM31 in the blood samples from 34 patients with AML and 34 healthy volunteers using qRT-PCR. The mRNA levels of TRIM31 in human bone marrow stromal cells (HS-5) and five AML cell lines were also detected. Loss/gain-of-function assays were performed to assess the role of TRIM31 in AML cells proliferation, apoptosis and sensitivity to daunorubicin. The expression levels of pro-caspase 3, cleaved caspase 3, Wnt3a, β-catenin, cyclin D1 and c-Myc were measured using Western blot. TRIM31 expression levels were significantly up-regulated in AML patients and cell lines. Knockdown of TRIM31 suppressed cell proliferation and promoted apoptosis in AML-5 and U937 cells. The IC50 of daunorubicin was significantly decreased in TRIM31 siRNA (si-TRIM31) transfected cells. Oppositely, induced cell proliferation and decreased cell apoptosis were observed in pcDNA-3.1-TRIM31 transfected cells. Furthermore, knockdown of TRIM31 suppressed the activation of Wnt/β-catenin pathway in AML cells. Activation of Wnt/β-catenin pathway by LiCl abolished the effects of si-TRIM31 on cell proliferation, apoptosis and sensitivity to daunorubicin in AML cells. In conclusion, the results indicated that TRIM31 promoted leukemogenesis and chemoresistance to daunorubicin in AML. The oncogenic role of TRIM31 in AML was mediated by the Wnt/β-catenin pathway. Thus, TRIM31 might serve as a therapeutic target for the AML treatment.
Highlights
Acute myeloid leukemia (AML) is a kind of leukemia that starts in the myeloid cells, which have the capacities of self-renewing, sustaining malignant populations and producing subclones [1]
The results showed that highexpression levels of TRIM31 were observed in AML cell lines, especially in AML-5 and U937 cells (Figure 1B,C)
We found that knockdown of TRIM31 significantly promoted caspase-3 activity in AML-5 and U937 cells, respectively, as compared with the si-con group (Figure 2E,F)
Summary
Acute myeloid leukemia (AML) is a kind of leukemia that starts in the myeloid cells, which have the capacities of self-renewing, sustaining malignant populations and producing subclones [1]. AML is the most common acute leukemia and can be very fatal in a short period without suitable intervention. Chemotherapy is a standard treatment option applied in both induction and consolidation phases to destroy leukemic cells [6]. This therapy usually presents high toxicity and high risk of recurrence due to the chemoresistance of AML stem cells [4]. Considering these alarming challenges, it is imperative to develop appropriate intervention for AML progression and chemoresistance
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