MicroRNA profiling in K-562 cells under imatinib treatment

Turrini, Eleonora; Haenisch, Sierk; Laechelt, Sandra; Diewock, Tobias; Bruhn, Oliver; Cascorbi, Ingolf

doi:10.1097/fpc.0b013e328350012b

Cited by 70 publications

(28 citation statements)

References 24 publications

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“…Interaction between miRNA-212-3p and ABCG2 was also demonstrated in an earlier study (Turrini et al, 2012). ABCG2 is an important efflux transporter implicated in chemo-resistance of tumor stem cells (Mo and Zhang, 2012).…”

Section: Discussionsupporting

confidence: 77%

SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients

Haenisch¹,

Zhao²,

Chhibber³

et al. 2015

Neurobiology of Disease

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MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally control the expression of their target genes via RNA interference. There is increasing evidence that expression of miRNAs is dysregulated in neuronal disorders, including epilepsy, a chronic neurological disorder characterized by spontaneous recurrent seizures. Mesial temporal lobe epilepsy (MTLE) is a common type of focal epilepsy in which disease-induced abnormalities of hippocampal neurogenesis in the subgranular zone as well as gliosis and neuronal cell loss in the cornu ammonis area are reported. We hypothesized that in MTLE altered miRNA-mediated regulation of target genes could be involved in hippocampal cell remodeling. A miRNA screen was performed in hippocampal focal and non-focal brain tissue samples obtained from the temporal neocortex (both n=8) of MTLE patients. Out of 215 detected miRNAs, two were differentially expressed (hsa-miR-34c-5p: mean increase of 5.7 fold (p=0.014), hsa-miR-212-3p: mean decrease of 76.9% (p=0.0014)). After in-silico target gene analysis and filtering, reporter gene assays confirmed RNA interference for hsa-miR-34c-5p with 3′-UTR sequences of GABRA3, GRM7 and GABBR2 and for hsa-miR-212-3p with 3′-UTR sequences of SOX11, MECP2, ADCY1 and ABCG2. Reporter gene assays with mutated 3′-UTR sequences of the transcription factor SOX11 identified two different binding sites for hsa-miR-212-3p and its primary transcript partner hsa-miR-132-3p. Additionally, there was an inverse time-dependent expression of Sox11 and miR-212-3p as well as miR-132-3p in rat neonatal cortical neurons. Transfection of neurons with anti-miRs for miR-212-3p and miR-132-3p suggest that both miRNAs work synergistically to control Sox11 expression. Taken together, these results suggest that differential miRNA expression in neurons could contribute to an altered function of the transcription factor SOX11 and other genes in the setting of epilepsy, resulting not only in impaired neural differentiation, but also in imbalanced neuronal excitability and accelerated drug export.

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Section: Discussionsupporting

confidence: 77%

SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients

Haenisch¹,

Zhao²,

Chhibber³

et al. 2015

Neurobiology of Disease

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“…In MCF7 breast cancer cells and in K562 CML cells, miR-212 targets the ABCG2 3′-UTR, resulting in diminished ABCG2 expression and decreased resistance to mitoxantrone or imatinib, respectively [85,86]. In a similar manner, Dong et al [87] found that miR-31 targets the 3′-UTR of the ABCB9 mRNA transcript, causing its downregulation and decreased resistance to cisplatin in non-small-cell lung cancer (NSCLC) cells.…”

Section: Roles Of Mirna Species In Mediating Intrinsic and Acquired Resmentioning

confidence: 99%

Micrornas as Pharmacogenomic Biomarkers for Drug Efficacy and Drug Safety Assessment

et al. 2015

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Much evidence has documented that microRNAs (miRNAs) play an important role in the modulation of interindividual variability in the production of drug metabolizing enzymes and transporters (DMETs) and nuclear receptors (NRs) through multidirectional interactions involving environmental stimuli/stressors, the expression of miRNA molecules and genetic polymorphisms. MiRNA expression has been reported to be affected by drugs and miRNAs themselves may affect drug metabolism and toxicity. In cancer research, miRNA biomarkers have been identified to mediate intrinsic and acquired resistance to cancer therapies. In drug safety assessment, miRNAs have been found associated with cardiotoxicity, hepatotoxicity and nephrotoxicity. This review article summarizes published studies to show that miRNAs can serve as early biomarkers for the evaluation of drug efficacy and drug safety.

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“…Some in vitro studies have shown that miR-328 inhibits the expression of BCRP mRNA and protein2829. We previously demonstrated that miR-328 levels negatively correlated with BCRP mRNA and protein expression levels in the human placenta7.…”

Section: Discussionmentioning

confidence: 91%

“…The methylation patterns of several CpG dinucleotides proximal to two C/EBPα-binding sites in the miR-328 5′-flanking region negatively correlated with miR-328 levels, and positively correlated with BCRP protein levels in human placental samples7. Other miRNAs such as miR-519c, miR-520h, and miR-212 also regulate the expression of BCRP2829. Li et al .…”

Section: Discussionmentioning

confidence: 99%

Circulating intestine-derived exosomal miR-328 in plasma, a possible biomarker for estimating BCRP function in the human intestines

Gotanda

Hirota

Saito

et al. 2016

Sci Rep

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A variant in the breast cancer resistance protein (BCRP) gene, 421C> A is a useful biomarker for describing large inter-individual differences in the pharmacokinetics of sulfasalazine (SASP), a BCRP substrate. However, large intra-genotypic variability still exists in spite of the incorporation of this variant into the pharmacokinetics of SASP. Since miR-328 negatively regulates BCRP expression in human tissues, we hypothesized that exosomal miR-328 in plasma, which leaks from the intestines, is a possible biomarker for estimating BCRP activity in the human intestines. We established an immunoprecipitation-based quantitative method for circulating intestine-derived miR-328 in plasma using an anti-glycoprotein A33 antibody. A clinical study was conducted with an open-label, non-randomized, and single-arm design involving 33 healthy participants. Intestine-derived exosomal miR-328 levels positively correlated (P < 0.05) with SASP AUC0-48, suggesting that subjects with high miR-328 levels have low intestinal BCRP activity, resulting in the high AUC of SASP. Circulating intestine-derived exosomal miR-328 in plasma has potential as a possible biomarker for estimating BCRP function in the human intestines.

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MicroRNA profiling in K-562 cells under imatinib treatment

Abstract: Our study suggests an association of imatinib treatment, miRNA downregulation and ABCG2 overexpression, possibly contributing to the mechanisms involved in imatinib distribution and response in CML therapy.

Cited by 70 publications

References 24 publications

SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients

SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients

Micrornas as Pharmacogenomic Biomarkers for Drug Efficacy and Drug Safety Assessment

Circulating intestine-derived exosomal miR-328 in plasma, a possible biomarker for estimating BCRP function in the human intestines

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