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MicroRNAs associated with the efficacy of photodynamic therapy in biliary tract cancer cell lines.

Wagner A, Mayr C, Bach D, Illig R, Plaetzer K, Berr F, Pichler M, Neureiter D, Kiesslich T - Int J Mol Sci (2014)

Bottom Line: Twenty miRs correlated significantly with either high or low PDT efficiency.PDT was particularly effective in cells with high levels of clustered miRs 25-93*-106b and (in case of miR-106b) a phenotype characterized by high expression of the mesenchymal marker vimentin and high proliferation (cyclinD1 and Ki67 expression).Insensitivity towards PDT was associated with high miR-200 family expression and (for miR-cluster 200a/b-429) expression of differentiation markers Ck19 and Ck8/18.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Muellner Hauptstrasse 48, Salzburg 5020, Austria. and.wagner@salk.at.

ABSTRACT
Photodynamic therapy (PDT) is a palliative treatment option for unresectable hilar biliary tract cancer (BTC) showing a considerable benefit for survival and quality of life with few side effects. Currently, factors determining the cellular response of BTC cells towards PDT are unknown. Due to their multifaceted nature, microRNAs (miRs) are a promising analyte to investigate the cellular mechanisms following PDT. For two photosensitizers, Photofrin® and Foscan®, the phototoxicity was investigated in eight BTC cell lines. Each cell line (untreated) was profiled for expression of n=754 miRs using TaqMan® Array Human MicroRNA Cards. Statistical analysis and bioinformatic tools were used to identify miRs associated with PDT efficiency and their putative targets, respectively. Twenty miRs correlated significantly with either high or low PDT efficiency. PDT was particularly effective in cells with high levels of clustered miRs 25-93*-106b and (in case of miR-106b) a phenotype characterized by high expression of the mesenchymal marker vimentin and high proliferation (cyclinD1 and Ki67 expression). Insensitivity towards PDT was associated with high miR-200 family expression and (for miR-cluster 200a/b-429) expression of differentiation markers Ck19 and Ck8/18. Predicted and validated downstream targets indicate plausible involvement of miRs 20a*, 25, 93*, 130a, 141, 200a, 200c and 203 in response mechanisms to PDT, suggesting that targeting these miRs could improve susceptibility to PDT in insensitive cell lines. Taken together, the miRNome pattern may provide a novel tool for predicting the efficiency of PDT and-following appropriate functional verification-may subsequently allow for optimization of the PDT protocol.

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Related in: MedlinePlus

Correlations of miR expression, viability and uptake-corrected phototoxicity after PDT with mTHPC or porfimer sodium. Pearsons correlation coefficient of 395 miRs expressed in at least four cell lines. 20 miRs correlate significantly either with PDT insensitivity (A, positive correlation with viability after PDT) or phototoxicity (B, negative correlation with viability after PDT). The color indicates positive (green) and negative (red) correlation coefficients. Correlations with viability and (uptake-corrected) phototoxicity show reciprocal trends. Of note, miR-20a* correlates significantly only with the three data sets for uptake-corrected phototoxicity. + Based on phototoxicity raw data as previously published [13], reproduced by permission of The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC; the full list of correlations is provided in supplementary file 2. * p < 0.05; ** p < 0.01; abbreviations: PF: porfimer sodium.
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ijms-15-20134-f002: Correlations of miR expression, viability and uptake-corrected phototoxicity after PDT with mTHPC or porfimer sodium. Pearsons correlation coefficient of 395 miRs expressed in at least four cell lines. 20 miRs correlate significantly either with PDT insensitivity (A, positive correlation with viability after PDT) or phototoxicity (B, negative correlation with viability after PDT). The color indicates positive (green) and negative (red) correlation coefficients. Correlations with viability and (uptake-corrected) phototoxicity show reciprocal trends. Of note, miR-20a* correlates significantly only with the three data sets for uptake-corrected phototoxicity. + Based on phototoxicity raw data as previously published [13], reproduced by permission of The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC; the full list of correlations is provided in supplementary file 2. * p < 0.05; ** p < 0.01; abbreviations: PF: porfimer sodium.

Mentions: The correlation of miR expression levels and viability after PDT using the three data sets for the two PSs in the BTC cell lines is shown in Figure 2. To correct for cell line-specific differences in PS uptake, correlation analysis between (uncorrected) viability data sets are supplemented by the corresponding photoxicity data corrected for the relative uptake of the respective PS. Only those miRs were included in the correlation analysis, which were quantifiable in at least four cell lines (n = 395).


MicroRNAs associated with the efficacy of photodynamic therapy in biliary tract cancer cell lines.

Wagner A, Mayr C, Bach D, Illig R, Plaetzer K, Berr F, Pichler M, Neureiter D, Kiesslich T - Int J Mol Sci (2014)

Correlations of miR expression, viability and uptake-corrected phototoxicity after PDT with mTHPC or porfimer sodium. Pearsons correlation coefficient of 395 miRs expressed in at least four cell lines. 20 miRs correlate significantly either with PDT insensitivity (A, positive correlation with viability after PDT) or phototoxicity (B, negative correlation with viability after PDT). The color indicates positive (green) and negative (red) correlation coefficients. Correlations with viability and (uptake-corrected) phototoxicity show reciprocal trends. Of note, miR-20a* correlates significantly only with the three data sets for uptake-corrected phototoxicity. + Based on phototoxicity raw data as previously published [13], reproduced by permission of The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC; the full list of correlations is provided in supplementary file 2. * p < 0.05; ** p < 0.01; abbreviations: PF: porfimer sodium.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264160&req=5

ijms-15-20134-f002: Correlations of miR expression, viability and uptake-corrected phototoxicity after PDT with mTHPC or porfimer sodium. Pearsons correlation coefficient of 395 miRs expressed in at least four cell lines. 20 miRs correlate significantly either with PDT insensitivity (A, positive correlation with viability after PDT) or phototoxicity (B, negative correlation with viability after PDT). The color indicates positive (green) and negative (red) correlation coefficients. Correlations with viability and (uptake-corrected) phototoxicity show reciprocal trends. Of note, miR-20a* correlates significantly only with the three data sets for uptake-corrected phototoxicity. + Based on phototoxicity raw data as previously published [13], reproduced by permission of The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC; the full list of correlations is provided in supplementary file 2. * p < 0.05; ** p < 0.01; abbreviations: PF: porfimer sodium.
Mentions: The correlation of miR expression levels and viability after PDT using the three data sets for the two PSs in the BTC cell lines is shown in Figure 2. To correct for cell line-specific differences in PS uptake, correlation analysis between (uncorrected) viability data sets are supplemented by the corresponding photoxicity data corrected for the relative uptake of the respective PS. Only those miRs were included in the correlation analysis, which were quantifiable in at least four cell lines (n = 395).

Bottom Line: Twenty miRs correlated significantly with either high or low PDT efficiency.PDT was particularly effective in cells with high levels of clustered miRs 25-93*-106b and (in case of miR-106b) a phenotype characterized by high expression of the mesenchymal marker vimentin and high proliferation (cyclinD1 and Ki67 expression).Insensitivity towards PDT was associated with high miR-200 family expression and (for miR-cluster 200a/b-429) expression of differentiation markers Ck19 and Ck8/18.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Muellner Hauptstrasse 48, Salzburg 5020, Austria. and.wagner@salk.at.

ABSTRACT
Photodynamic therapy (PDT) is a palliative treatment option for unresectable hilar biliary tract cancer (BTC) showing a considerable benefit for survival and quality of life with few side effects. Currently, factors determining the cellular response of BTC cells towards PDT are unknown. Due to their multifaceted nature, microRNAs (miRs) are a promising analyte to investigate the cellular mechanisms following PDT. For two photosensitizers, Photofrin® and Foscan®, the phototoxicity was investigated in eight BTC cell lines. Each cell line (untreated) was profiled for expression of n=754 miRs using TaqMan® Array Human MicroRNA Cards. Statistical analysis and bioinformatic tools were used to identify miRs associated with PDT efficiency and their putative targets, respectively. Twenty miRs correlated significantly with either high or low PDT efficiency. PDT was particularly effective in cells with high levels of clustered miRs 25-93*-106b and (in case of miR-106b) a phenotype characterized by high expression of the mesenchymal marker vimentin and high proliferation (cyclinD1 and Ki67 expression). Insensitivity towards PDT was associated with high miR-200 family expression and (for miR-cluster 200a/b-429) expression of differentiation markers Ck19 and Ck8/18. Predicted and validated downstream targets indicate plausible involvement of miRs 20a*, 25, 93*, 130a, 141, 200a, 200c and 203 in response mechanisms to PDT, suggesting that targeting these miRs could improve susceptibility to PDT in insensitive cell lines. Taken together, the miRNome pattern may provide a novel tool for predicting the efficiency of PDT and-following appropriate functional verification-may subsequently allow for optimization of the PDT protocol.

Show MeSH
Related in: MedlinePlus