miRNA-149* promotes cell proliferation and suppresses apoptosis by mediating JunB in T-cell acute lymphoblastic leukemia
Introduction
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of leukemia that is one of the most common malignancies diagnosed in children and adults [1], [2]. Various intracellular mechanisms have been indicated to contribute to disease pathogenesis and progression, including the NOTCH1, PI3K-Akt, and cyclin D3:CDK4/6 (cyclin-dependent kinase 4/6) pathways [3]. Nevertheless, the pathogenesis of T-ALL has not yet been fully elucidated and the therapeutic outcomes of patients with resistance or relapsed disease are still poor [4].
microRNAs (miRNAs) are a family of noncoding RNAs (ncRNAs) that regulate gene expression. Aberrant miRNA regulation has thus been shown to play multiple roles in the pathogenesis of many diseases, including cancer [5], [6], [7]. miRNAs are 19–24 nt in length and are processed from large precursor hairpins approximately 70 nt long by the RNase III enzyme Dicer into mature miRNA and miRNA* duplexes (the complementary strands of miRNA that from miRNA/miRNA* duplexes) [8], [9], [10].
Microarray analyzes show that treatment with rapamycin greatly reduces the expression of miR-149* in the human T-ALL cell line Molt-4, suggesting that miR-149* may be involved in T-ALL pathogenesis. It has been shown that miR-149* serves as an oncogenic regulator in human melanoma [11]. However, the precise role of miR-149* in regulating gene expression and in mediating the pathogenesis of T-ALL remains unclear.
In the present study, we investigated the expression of miR-149* in cultured leukemia cell lines as well as in bone marrow cells derived from leukemia patients. In addition, the target gene for miR-149* was identified and the effects of miR-149* on biological properties of T-ALL cells were investigated. Our findings provide a potential approach for future miR-149*-targeting therapies for human T-ALL.
Section snippets
Cell culture
Cell lines, including T-ALL cell line Molt-4, human Burkitt’s lymphoma cell line Raja, human pre-B lymphoma cell line Nalm6, human chronic myeloid leukemia cell line K562, and human acute monocytic leukemia cell line THP-1 (all purchased from American Type Culture Collection, Manassas, VA, USA), were used in this study. The human T-cell lymphoblast-like cell line Jurkat was kindly provided by the Shanghai Cell Bank, Chinese Academy of Sciences, China. All of the normal control cells were
miRNA-149* was highly expressed in T-ALL cell lines
First, we examined the level of miRNA-149* in several cell lines, including the human T-ALL cell line Molt-4, human T-cell lymphoblast-like cell line Jurkat, B cell lymphoma Raja, human pre-B lymphoma cell line Nalm6, human chronic myelogenous leukemia cell line K562, and human acute monocytic leukemia cell line THP-1. As shown in Fig. 1A, the highest miRNA-149* expression level was detected in T-ALL cells Molt-4 and Jurkat cells (Molt-4, 4.10 ± 0.23; Jurkat, 3.26 ± 0.24; Nalm6, 2.69 ± 0.26; K562,
Discussion
miRNAs regulate gene expression post-transcriptionally and are associated with the pathogenesis of human cancer [7]. High levels of certain miRNAs, such as miR-21 [12], miR-24 [13], miR-9-5p [14], and miR-155-5P [14], etc., have been found in patients with acute leukemia and some of these overexpressed miRNA (e.g., miR-24, miR-9-5p, miR-155-5P) is associated with risks of relapse and poor outcome. However, certain miRNAs are found to be favorable factors for preventing disease progression [14],
Conclusion
The current study demonstrates that miRNA-149* may be a strong novel candidate oncogenic miRNA in T-ALL and that it targets the JunB gene. Our findings may be particularly important for understanding the aggressive properties of T-ALL and potentially lead to novel miRNA-149*-targeted treatment strategies.
Conflicts of interest
The authors declare that there are no conflicts of interest.
Acknowledgments
This study was supported by grants from the Heilongjiang Provincial Natural Science Foundation of China (No. AD200673) and the Doctoral Fund of the Ministry of Education of China (No. 20132307110022).
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2020, Biochemical and Biophysical Research CommunicationsCitation Excerpt :The expression level of miR-149* is highly expressed in T-ALL cells and T-ALL patients’ bone marrow samples. This ectopic expression inhibits cell apoptosis, reduces the proportion of G1 phase cells and promotes proliferation of T-ALL cells [27]. In this study, miRNA-149* was highly expressed in human melanoma tissues and melanoma cells.
miR-149* Suppresses Liver Cancer Progression by Down-Regulating Tumor Necrosis Factor Receptor 1–Associated Death Domain Protein Expression
2020, American Journal of PathologyCitation Excerpt :miR-149* plays an oncogenic role in human melanoma through suppressing glycogen synthase kinase-3α (GSK3α).23 miR-149* has previously been shown to directly target JunB, and thus promote cell growth and inhibit apoptosis in T-cell acute lymphoblastic leukaemia.41 Lin et al42 identified that miR-149* inhibits Akt1 and E2F1, leading to induction of apoptosis in human cancer cells.