MicroRNAs Associated with the Efficacy of Photodynamic Therapy in Biliary Tract Cancer Cell Lines

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2014 Nov 8

PMID 25380521

Citations 11

Authors

Andrej Wagner

Christian Mayr

Doris Bach

Romana Illig

Kristjan Plaetzer

Frieder Berr

Martin Pichler

Daniel Neureiter

Tobias Kiesslich

Affiliations

Soon will be listed here.

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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References

Curnow A, McIlroy B, Porter J, MacRobert A, Bown S . Enhancement of 5-aminolaevulinic acid-induced photodynamic therapy in normal rat colon using hydroxypyridinone iron-chelating agents. Br J Cancer. 1998; 78(10):1278-82. PMC: 2063198. DOI: 10.1038/bjc.1998.671. View

Cao L, Xue P, Lu H, Zheng Q, Wen Z, Shao Z . Hematoporphyrin derivative-mediated photodynamic therapy inhibits tumor growth in human cholangiocarcinoma in vitro and in vivo. Hepatol Res. 2009; 39(12):1190-7. DOI: 10.1111/j.1872-034X.2009.00569.x. View

Kiesslich T, Alinger B, Wolkersdorfer G, Ocker M, Neureiter D, Berr F . Active Wnt signalling is associated with low differentiation and high proliferation in human biliary tract cancer in vitro and in vivo and is sensitive to pharmacological inhibition. Int J Oncol. 2009; 36(1):49-58. View

Liu Q, Li R, Qian H, Wei J, Xie L, Shen J . Targeted delivery of miR-200c/DOC to inhibit cancer stem cells and cancer cells by the gelatinases-stimuli nanoparticles. Biomaterials. 2013; 34(29):7191-203. DOI: 10.1016/j.biomaterials.2013.06.004. View

Li N, Muthusamy S, Liang R, Sarojini H, Wang E . Increased expression of miR-34a and miR-93 in rat liver during aging, and their impact on the expression of Mgst1 and Sirt1. Mech Ageing Dev. 2011; 132(3):75-85. DOI: 10.1016/j.mad.2010.12.004. View

Kleban J, Mikes J, Horvath V, Sackova V, Hofmanova J, Kozubik A . Mechanisms involved in the cell cycle and apoptosis of HT-29 cells pre-treated with MK-886 prior to photodynamic therapy with hypericin. J Photochem Photobiol B. 2008; 93(2):108-18. DOI: 10.1016/j.jphotobiol.2008.07.007. View

Witzigmann H, Berr F, Ringel U, Caca K, Uhlmann D, Schoppmeyer K . Surgical and palliative management and outcome in 184 patients with hilar cholangiocarcinoma: palliative photodynamic therapy plus stenting is comparable to r1/r2 resection. Ann Surg. 2006; 244(2):230-9. PMC: 1602149. DOI: 10.1097/01.sla.0000217639.10331.47. View

Gammon L, Biddle A, Heywood H, Johannessen A, Mackenzie I . Sub-sets of cancer stem cells differ intrinsically in their patterns of oxygen metabolism. PLoS One. 2013; 8(4):e62493. PMC: 3640080. DOI: 10.1371/journal.pone.0062493. View

Wang X, El Naqa I . Prediction of both conserved and nonconserved microRNA targets in animals. Bioinformatics. 2007; 24(3):325-32. DOI: 10.1093/bioinformatics/btm595. View

10.

Miyake M, Ishii M, Kawashima K, Kodama T, Sugano K, Fujimoto K . siRNA-mediated knockdown of the heme synthesis and degradation pathways: modulation of treatment effect of 5-aminolevulinic acid-based photodynamic therapy in urothelial cancer cell lines. Photochem Photobiol. 2009; 85(4):1020-7. DOI: 10.1111/j.1751-1097.2009.00543.x. View

11.

Zhuang S, Kochevar I . Singlet oxygen-induced activation of Akt/protein kinase B is independent of growth factor receptors. Photochem Photobiol. 2003; 78(4):361-71. DOI: 10.1562/0031-8655(2003)078<0361:soaopk>2.0.co;2. View

12.

Ferrario A, Rucker N, Wong S, Luna M, Gomer C . Survivin, a member of the inhibitor of apoptosis family, is induced by photodynamic therapy and is a target for improving treatment response. Cancer Res. 2007; 67(10):4989-95. DOI: 10.1158/0008-5472.CAN-06-4785. View

13.

Koukourakis M, Giatromanolaki A, Skarlatos J, Corti L, Blandamura S, Piazza M . Hypoxia inducible factor (HIF-1a and HIF-2a) expression in early esophageal cancer and response to photodynamic therapy and radiotherapy. Cancer Res. 2001; 61(5):1830-2. View

14.

Nonaka M, Ikeda H, Inokuchi T . Inhibitory effect of heat shock protein 70 on apoptosis induced by photodynamic therapy in vitro. Photochem Photobiol. 2004; 79(1):94-8. View

15.

Pervaiz S, Clement M . Superoxide anion: oncogenic reactive oxygen species?. Int J Biochem Cell Biol. 2007; 39(7-8):1297-304. DOI: 10.1016/j.biocel.2007.04.007. View

16.

Lo W, Yu C, Chiou G, Chen Y, Huang P, Chien C . MicroRNA-200c attenuates tumour growth and metastasis of presumptive head and neck squamous cell carcinoma stem cells. J Pathol. 2011; 223(4):482-95. DOI: 10.1002/path.2826. View

17.

Kemmerling R, Alinger B, Dietze O, Bosmuller H, Ocker M, Wolkersdorfer G . Association of stem cell marker expression pattern and survival in human biliary tract cancer. Int J Oncol. 2012; 41(2):511-22. DOI: 10.3892/ijo.2012.1477. View

18.

Meng S, Cao J, Zhang B, Zhou Q, Shen C, Wang C . Downregulation of microRNA-126 in endothelial progenitor cells from diabetes patients, impairs their functional properties, via target gene Spred-1. J Mol Cell Cardiol. 2012; 53(1):64-72. DOI: 10.1016/j.yjmcc.2012.04.003. View

19.

Pichler M, Ress A, Winter E, Stiegelbauer V, Karbiener M, Schwarzenbacher D . MiR-200a regulates epithelial to mesenchymal transition-related gene expression and determines prognosis in colorectal cancer patients. Br J Cancer. 2014; 110(6):1614-21. PMC: 3960623. DOI: 10.1038/bjc.2014.51. View

20.

Kushibiki T . Photodynamic therapy induces microRNA-210 and -296 expression in HeLa cells. J Biophotonics. 2009; 3(5-6):368-72. DOI: 10.1002/jbio.200900082. View