Changes in the Expression of miR-381 and miR-495 Are Inversely Associated with the Expression of the MDR1 Gene and Development of Multi-Drug Resistance

Xu, Yan; Ohms, Stephen; Li, Zhen; Qiao, Wei; Gong, Guangming; Hu, Yiqiao; Mao, Zhiyong; Shannon, M. Frances; Fan, Jun

doi:10.1371/journal.pone.0082062

Cited by 81 publications

(70 citation statements)

References 45 publications

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“…In addition, miR-381, which is present in the p53/PTTG1 negative feedback loop, can inhibit the growth of pituitary adenomas (23). miR-381 is closely related to MDR1 gene and plays an important role in multidrug resistance (24). Together with miR-424, miR-381 can target WEE1 gene to inhibit the activity of renal cancer Cdc2 cells (25).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑381 protects myocardial cell function in children and mice with viral myocarditis via targeting cyclooxygenase‑2 expression

Zhang

Sun

et al. 2018

Exp Ther Med

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Abstract. The present study aimed to determine the expression of cyclooxygenase (COX)-2 and microRNA (miRNA/miR)-381 in the blood of children with viral myocarditis (VM), and investigate the association between COX-2 and miR-381 in the occurrence and development of the disease using a mouse model. A total of 26 children with VM (15 boys and 11 girls) were included in the present study. Peripheral blood was collected from all children. The mouse model of VM was constructed by coxsackievirus B3 (CVB3) infection. Peripheral blood and myocardial tissues were collected from all mice for analysis. Reverse transcription-quantitative polymerase chain reaction was used to determine the expression of COX-2 mRNA and miR-381 in serum and myocardial tissues. ELISA was used to measure the content of COX-2 protein in serum from humans and mice, and western blotting was employed to determine the expression of COX-2 protein in myocardial tissues from mice. Contents of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) were evaluated using an automatic biochemical analyzer. A dual luciferase assay was conducted to identify interactions between COX-2 mRNA and miR-381. Children with VM had increased COX-2 levels and decreased miR-381 expression in peripheral blood, compared with those who had recovered from VM. CVB3 infection resulted in damage in the myocardium of mice, and elevated CK-MB and LDH contents. VM model mice exhibited increased COX-2 levels and decreased miR-381 expression in peripheral blood and myocardial tissues compared with normal mice. miR-381 binds to the 3'-untranslated seed regions of both human and mouse COX-2 mRNA to regulate their expression. The present study demonstrated that children with VM have decreased miR-381 expression and elevated COX-2 expression in peripheral blood. miR-381 may inhibit myocardial cell damage caused by CVB3 infection and protect myocardial cell function by targeting COX-2 expression. IntroductionThe incidence of viral myocarditis (VM) is gradually increased in recent years, and attracts the attention of more and more scholars (1). Coxsackievirus B3 (CVB3) is one of the most common viruses that cause VM (2). VM can develop into acute heart failure (3,4). According to available clinical studies, the mortality rate of VM in young people is as high as 21%, and sudden deaths caused by VM or fatal ventricular arrhythmias in children account for about 20% (5,6). However, there have been few effective therapies for VM by now. Current treatment for VM is still focused on the control of cardiac arrhythmia and heart failure. Therefore, it is necessary to study the molecular mechanism of VM.VM is a common infectious disease in pediatric clinical practice. It is caused by viral infection or disturbance of autoimmune system, and characterized by localized or diffuse acute or chronic inflammatory lesions of the myocardium (1,7). In inflammation, cyclooxygenase (COX), especially COX-2 in the COX family, plays an important role. COX-2 is produced after induction by external stimuli (physical...

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑381 protects myocardial cell function in children and mice with viral myocarditis via targeting cyclooxygenase‑2 expression

Zhang

Sun

et al. 2018

Exp Ther Med

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“…Hence, miR-429 may be a potential cancer therapeutic target. miR-381 were strongly downregulated in MDR cells (K562/ADM) by targeting the 3'-uTR of the MDR1 gene and restoring expression of miR-381 in K562/ADM cells was correlated with reduced expression of the MDR1 gene and its protein product, P-gp and increased drug uptake by the cells (29). Additionally, the ubiquitin-specific protease 2a (usP2a) induced drug resistance in PCa cells, and inhibition of miR-34b made usP2a…”

Section: Discussionmentioning

confidence: 99%

Exosome-derived microRNAs contribute to prostate cancer chemoresistance

Yang

Guan

et al. 2016

International Journal of Oncology

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Abstract. Certain microRNAs (miRNAs) play a key role in cancer cell chemoresistance. However, the pleiotropic functions of exosome-derived miRNAs on developing chemoresistance remain unknown. In the present study, we aimed to construct potential networks of miRNAs, which derived from the exosome of chemoresistant prostate cancer (PCa) cells, with their known target genes using miRNA expression profiling and bioinformatic tools. Global miRNA expression profiles were measured by microarray. Twelve miRNAs were initially selected and validated by qRT-PCR. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of miRNAs and their targer genes from the selected KEGG pathway 'PCa progression (hsa05215)' were visualized by Cytoscape software. We identified 29 deregulated miRNAs, including 19 upregulated and 10 downregulated, in exosome samples derived from two kinds of paclitaxel resistance PCa cells (PC3-TXR and DU145-TXR) compared with their parental cells (PC3 and DU145). The enrichment results of deregulated miRNAs and known target genes showed that a few pathways were correlated with several critical cell signaling pathways. We found that hub hsa-miR3176, -141-3p, -5004-5p, -16-5p, -3915, -488-3p, -23c, -3673 and -3654 were potential targets to hub gene androgen receptor (AR) and phosphatase and tensin homolog (PTEN). Hub gene T-cell factors/lymphoid enhancer-binding factors 4 (TCF4) target genes were mainly regulated by hub hsa-miR-32-5, -141-3p, -606, -381 and -429. These results may provide a linkage between PCa chemoresistance and exosome regulatory networks and thus lead us to propose that AR, PTEN and TCF4 genes may be the important genes which are regulated by exosome miRNAs in chemoresistance cancer cells.

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“…18 MiR-381 and miR-495 modulated the MDR phenotype of leukemia K562/ ADM cells and were associated inversely with the expression of the MDR1 gene and its protein product, P-glycoprotein. 19 Altered expression of miR-331-5p and miR-27a were correlated with leukemia cell resistance and relapse. 20 MiR-138 also reversed MDR of leukemia HL-60/VCR cells and promoted adriamycin-induced cell apoptosis.…”

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confidence: 99%

Alpha-2, 3-sialyltransferases regulate the multidrug resistance of chronic myeloid leukemia through miR-4701-5p targeting ST3GAL1

Luo

Dong

et al. 2016

Laboratory Investigation

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The aberrant sialylation profile on the surface of leukemia cells has been recognized for its potential diagnostic value towards assessing leukemia multidrug resistance (MDR). MicroRNAs as endogenous regulators of gene expression have been implicated in treating MDR. In this study, we describe the differential expressional profiles of α-2, 3-sialyltransferases (ST) and miR-4701-5p in three pairs of chronic myeloid leukemia (CML) cell lines and 48 clinical samples of bone marrow mononuclear cells from CML patients. The altered expression level of ST3GAL1 was found corresponding to the drugresistant phenotype (with and without adriamycin resistance) of CML cell lines both in vitro and in vivo. Further the results showed that miR-4701-5p directly targeted ST3GAL1 to reduce CML cells resistance to multiple chemotherapeutics in vitro and to convert tumor cells from adriamycin resistant to susceptible in vivo of mice. These results indicate that differential expression of α-2,3 ST is involved in MDR of CML, and that miR-4701-5p regulates the susceptibility of CML cells to multiple drugs, at least in part, through targeting ST3GAL1.

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Changes in the Expression of miR-381 and miR-495 Are Inversely Associated with the Expression of the MDR1 Gene and Development of Multi-Drug Resistance

Cited by 81 publications

References 45 publications

MicroRNA‑381 protects myocardial cell function in children and mice with viral myocarditis via targeting cyclooxygenase‑2 expression

MicroRNA‑381 protects myocardial cell function in children and mice with viral myocarditis via targeting cyclooxygenase‑2 expression

Exosome-derived microRNAs contribute to prostate cancer chemoresistance

Alpha-2, 3-sialyltransferases regulate the multidrug resistance of chronic myeloid leukemia through miR-4701-5p targeting ST3GAL1

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