Dataset Information

Down-regulated miR-331-5p and miR-27a are associated with chemotherapy resistance and relapse in leukaemia.

ABSTRACT: Multidrug resistance (MDR) and disease relapse are challenging clinical problems in the treatment of leukaemia. Relapsed disease is frequently refractory to chemotherapy and exhibits multiple drug resistance. Therefore, it is important to identify the mechanism by which cancer cells develop resistance. In this study, we used microRNA (miRNA) microarray and qRT-PCR approaches to investigate the expression of miRNAs in three leukaemia cell lines with different degrees of resistance to doxorubicin (DOX) compared with their parent cell line, K562. The expression of miR-331-5p and miR-27a was inversely correlated with the expression of a drug-resistant factor, P-glycoprotein (P-gp), in leukaemia cell lines with gradually increasing resistance. The development of drug resistance is regulated by the expression of the P-gp. Transfection of the K562 and, a human promyelocytic cell line (HL) HL60 DOX-resistant cells with miR-331-5p and miR-27a, separately or in combination, resulted in the increased sensitivity of cells to DOX, suggesting that correction of altered expression of miRNAs may be used for therapeutic strategies to overcome leukaemia cell resistance. Importantly, miR-331-5p and miR-27a were also expressed at lower levels in a panel of relapse patients compared with primary patients at diagnosis, further illustrating that leukaemia relapse might be a consequence of deregulation of miR-331-5p and miR-27a.

SUBMITTER: Feng DD

PROVIDER: S-EPMC4394226 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Down-regulated miR-331-5p and miR-27a are associated with chemotherapy resistance and relapse in leukaemia.

Feng Dan-Dan DD Zhang Hua H Zhang Peng P Zheng Yu-Sheng YS Zhang Xing-Ju XJ Han Bo-Wei BW Luo Xue-Qun XQ Xu Ling L Zhou Hui H Qu Liang-Hu LH Chen Yue-Qin YQ

Journal of cellular and molecular medicine 20111001 10

Multidrug resistance (MDR) and disease relapse are challenging clinical problems in the treatment of leukaemia. Relapsed disease is frequently refractory to chemotherapy and exhibits multiple drug resistance. Therefore, it is important to identify the mechanism by which cancer cells develop resistance. In this study, we used microRNA (miRNA) microarray and qRT-PCR approaches to investigate the expression of miRNAs in three leukaemia cell lines with different degrees of resistance to doxorubicin ...[more]

PMID: 21070600

Similar Datasets

Project description:Alzheimer's disease (AD) is currently ranked as the third leading cause of death for eldly people, just behind heart disease and cancer. Autophagy is declined with aging. Our study determined the biphasic changes of miR-331-3p and miR-9-5p associated with AD progression in APPswe/PS1dE9 mouse model and demonstrated inhibiting miR-331-3p and miR-9-5p treatment prevented AD progression by promoting the autophagic clearance of amyloid beta (Aβ). Methods: The biphasic changes of microRNAs were obtained from RNA-seq data and verified by qRT-PCR in early-stage (6 months) and late-stage (12 months) APPswe/PS1dE9 mice (hereinafter referred to as AD mice). The AD progression was determined by analyzing Aβ levels, neuron numbers (MAP2+) and activated microglia (CD68+IBA1+) in brain tissues using immunohistological and immunofluorescent staining. MRNA and protein levels of autophagic-associated genes (Becn1, Sqstm1, LC3b) were tested to determine the autophagic activity. Morris water maze and object location test were employed to evaluate the memory and learning after antagomirs treatments in AD mice and the Aβ in the brain tissues were determined. Results: MiR-331-3p and miR-9-5p are down-regulated in early-stage of AD mice, whereas up-regulated in late-stage of AD mice. We demonstrated that miR-331-3p and miR-9-5p target autophagy receptors Sequestosome 1 (Sqstm1) and Optineurin (Optn), respectively. Overexpression of miR-331-3p and miR-9-5p in SH-SY5Y cell line impaired autophagic activity and promoted amyloid plaques formation. Moreover, AD mice had enhanced Aβ clearance, improved cognition and mobility when treated with miR-331-3p and miR-9-5p antagomirs at late-stage. Conclusion: Our study suggests that using miR-331-3p and miR-9-5p, along with autophagic activity and amyloid plaques may distinguish early versus late stage of AD for more accurate and timely diagnosis. Additionally, we further provide a possible new therapeutic strategy for AD patients by inhibiting miR-331-3p and miR-9-5p and enhancing autophagy.

Project description:BackgroundMicroRNAs (miRNAs) play a vital role in tuberculosis (TB). Vitamin D receptor (VDR), an miRNA target gene, and its ligand, vitamin D3 (VitD3), have been reported to exert protective effects against TB. However, whether miRNAs can affect the progression of TB by targeting VDR has not been reported.Materials and methodsResearch subjects were selected according to defined inclusion criteria. A clinical database of 360 samples was established, including the subjects' demographic information, miRNA expression profiles and cellular experimental results. Two candidate miRNAs, miR-27a-3p, and miR-30b-5p, were identified by a high-throughput sequencing screen and validated by qRT-PCR assays. Univariate and multivariate statistical analyses were performed. VDR and NF-kB p65 protein levels were detected by Western blot assays. Proinflammatory cytokine expression levels were detected by enzyme-linked immunosorbent assay (ELISA). Luciferase assays and fluorescence-activated cell sorting (FACS) were further applied to elucidate the detailed mechanisms.ResultsDifferential miRNA expression profiles were obtained, and miR-27a-3p and miR-30b-5p were highly expressed in patients with TB. These results showed that the two miRNAs were able to induce M1 macrophage differentiation and inhibit M2 macrophage differentiation. Further experiments showed that the two miRNAs decreased the VDR protein level and increased proinflammatory cytokine secretion by macrophages. Mechanistically, the miRNAs targeted the 3' untranslated region (3'UTR) of the VDR mRNA and thereby downregulated VDR protein levels by post-transcriptional regulation. Then, due to the reduction in VDR protein levels, the NF-kB inflammatory cytokine signaling pathway was activated, thus promoting the progression of TB.ConclusionOur study not only identified differentially expressed miRNAs between the TB and control groups but also revealed that miR-27a-3p and miR-30b-5p regulate proinflammatory cytokine secretion and macrophage differentiation through VDR in macrophages. Thus, these two miRNAs influence the progression of TB.

Dataset Information

Down-regulated miR-331-5p and miR-27a are associated with chemotherapy resistance and relapse in leukaemia.

Publications

Down-regulated miR-331-5p and miR-27a are associated with chemotherapy resistance and relapse in leukaemia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets