miR-134 increases the antitumor effects of cytarabine by targeting Mnks in acute myeloid leukemia cells

Chen, Kankan; Chen, Yue; Chen, Zhi; Shi, Yuye; He, Zhengmei; Ding, Banghe; Yu, Liang

doi:10.2147/ott.s143465

Cited by 16 publications

(19 citation statements)

References 26 publications

(23 reference statements)

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“…Decreases cell migration and invasion. Drug resistance [ 130 ] miR-221/ -222 MCF-7 (Tamoxifen resistant) MCF-7 (Tamoxifen-sensitive) P27 and ERα Enhances tamoxifen resistance in recipient cells. Drug resistance [ 68 ] miR-223 IL-4-activated macrophages MDA-MB-231 Mef2c- β-catenin Promotes the invasion of breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Effect of exosomal miRNA on cancer biology and clinical applications

et al. 2018

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Exosomes, extracellular vesicles with diameters ranging from 30 to 150 nm, are widely present in various body fluids. Recently, microRNAs (miRNAs) have been identified in exosomes, the biogenesis, release, and uptake of which may involve the endosomal sorting complex required for transport (ESCRT complex) and relevant proteins. After release, exosomes are taken up by neighboring or distant cells, and the miRNAs contained within modulate such processes as interfering with tumor immunity and the microenvironment, possibly facilitating tumor growth, invasion, metastasis, angiogenesis and drug resistance. Therefore, exosomal miRNAs have a significant function in regulating cancer progression. Here, we briefly review recent findings regarding tumor-derived exosomes, including RNA sorting and delivering mechanism. We then describe the intercommunication occurring between different cells via exosomal miRNAs in tumor microenvironmnt, with impacts on tumor proliferation, vascularization, metastasis and other biological characteristics. Finally, we highlight the potential role of these molecules as biomarkers in cancer diagnosis and prognosis and tumor resistance to therapeutics.

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Section: Introductionmentioning

confidence: 99%

Effect of exosomal miRNA on cancer biology and clinical applications

et al. 2018

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“…Consistent with our hypothesis, we found that UNC1999treated cells upregulated four miRNAs (miR-494-3p, miR-130a-3p, miR-134-5p and miR-192-5p) that could functionally downregulate methionine cycling-associated genes such as MAT2A, MAT2B, CBS and CTH. Notably, these miRNAs have been reported in the context of several other cancer types [39][40][41][42][43][44][45][46][47][48] .…”

Section: Discussionmentioning

confidence: 96%

A distinct metabolic response characterizes sensitivity to EZH2 inhibition in multiple myeloma

et al. 2021

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Multiple myeloma (MM) is a heterogeneous haematological disease that remains clinically challenging. Increased activity of the epigenetic silencer EZH2 is a common feature in patients with poor prognosis. Previous findings have demonstrated that metabolic profiles can be sensitive markers for response to treatment in cancer. While EZH2 inhibition (EZH2i) has proven efficient in inducing cell death in a number of human MM cell lines, we hereby identified a subset of cell lines that despite a global loss of H3K27me3, remains viable after EZH2i. By coupling liquid chromatography-mass spectrometry with gene and miRNA expression profiling, we found that sensitivity to EZH2i correlated with distinct metabolic signatures resulting from a dysregulation of genes involved in methionine cycling. Specifically, EZH2i resulted in a miRNA-mediated downregulation of methionine cycling-associated genes in responsive cells. This induced metabolite accumulation and DNA damage, leading to G2 arrest and apoptosis. Altogether, we unveiled that sensitivity to EZH2i in human MM cell lines is associated with a specific metabolic and gene expression profile post-treatment.

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“…Especially, high dose Ara-C is a part of an induction regimen as a first-line therapy for AML [ 36 ]. However, the resistance of AML cells to Ara-C chemotherapy is one of the most important reasons for relapse or chemo-refractoriness in AML patients [ 37 ]. For that reason, combination therapy has become the standard therapy for the treatment of several different cancers [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Radotinib enhances cytarabine (Ara-C)-induced acute myeloid leukemia cell death

et al. 2020

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Background Acute myeloid leukemia (AML) is a heterogeneous disease that frequently relapses after standard chemotherapy. Therefore, there is a need for the development of novel chemotherapeutic agents that could treat AML effectively. Radotinib, an oral BCR-ABL tyrosine kinase inhibitor, was developed as a drug for the treatment of chronic myeloid leukemia. Previously, we reported that radotinib exerts increased cytotoxic effects towards AML cells. However, little is known about the effects of combining radotinib with Ara-C, a conventional chemotherapeutic agent for AML, with respect to cell death in AML cells. Therefore, we investigated combination effects of radotinib and Ara-C on AML in this study. Methods Synergistic anti-cancer effects of radotinib and Ara-C in AML cells including HL60, HEL92.1.7, THP-1 and bone marrow cells from AML patients have been examined. Diverse cell biological assays such as cell viability assay, Annexin V-positive cells, caspase-3 activity, cell cycle distribution, and related signaling pathway have been performed. Results The combination of radotinib and Ara-C was found to induce AML cell apoptosis, which involved the mitochondrial pathway. In brief, combined radotinib and Ara-C significantly induced Annexin V-positive cells, cytosolic cytochrome C, and the pro-apoptotic protein Bax in AML cells including HL60, HEL92.1.7, and THP-1. In addition, mitochondrial membrane potential and Bcl-xl protein were markedly decreased by radotinib and Ara-C. Moreover, this combination induced caspase-3 activity. Cleaved caspase-3, 7, and 9 levels were also increased by combined radotinib and Ara-C. Additionally, radotinib and Ara-C co-treatment induced G0/G1 arrest via the induction of CDKIs such as p21 and p27 and the inhibition of CDK2 and cyclin E. Thus, radotinib/Ara-C induces mitochondrial-dependent apoptosis and G0/G1 arrest via the regulation of the CDKI–CDK–cyclin cascade in AML cells. In addition, our results showed that combined treatment with radotinib and Ara-C inhibits AML cell growth, including tumor volumes and weights in vivo. Also, the combination of radotinib and Ara-C can sensitize cells to chemotherapeutic agents such as daunorubicin or idarubicin in AML cells. Conclusions Therefore, our results can be concluded that radotinib in combination with Ara-C possesses a strong anti-AML activity.

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miR-134 increases the antitumor effects of cytarabine by targeting Mnks in acute myeloid leukemia cells

Cited by 16 publications

References 26 publications

Effect of exosomal miRNA on cancer biology and clinical applications

Effect of exosomal miRNA on cancer biology and clinical applications

A distinct metabolic response characterizes sensitivity to EZH2 inhibition in multiple myeloma

Radotinib enhances cytarabine (Ara-C)-induced acute myeloid leukemia cell death

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