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

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.

Expression of serum miR-200a, miR-200b, and miR-200c as candidate biomarkers in epithelial ovarian cancer and their association with clinicopathological features

“…with the atypical expression of miR-200a, miR-200b, and miR200c. Although our investigations were in consonance with several others in varied types of cancers (such as Prostate [15], Breast [37,38], Ovary [16,39,40], NSCLC [10,41], Bladder [42], Hepatocellular [35,43], Pancreatic [44], Biliary duct [45], Endometrial endometrioid [46], Anaplastic thyroid [47]) and discrete populations throughout the world [16,48], few studies suggested otherwise such as the study by Xu et al [49] which indicated that the expression levels of miR-200a were significantly down-regulated in late-stage disease (FIGO III ? IV) compared with early stage (FIGO I ?…”

Inhibition of miRNA‑21 attenuates the proliferation and metastasis of human osteosarcoma by upregulating PTEN

“…As a group of non-coding RNAs, miRNAs exist in a wide variety of organisms and have been demonstrated to have important biological functions with complicated mechanisms of action, each having single or multiple target genes to regulate (14)(15)(16). miRNA-21 is a ubiquitous miRNA, which is expressed at abnormal levels in numerous types of cancer, including colorectal cancer, bile duct carcinoma, lymphoma, multiple myeloma and glioma, suggesting that it is an oncogene (15)(16)(17).…”

Involvement of Bim in Photofrin-Mediated Photodynamically Induced Apoptosis

“…Electric field-assisted delivery of photofrin, electroporation, to the breast adenocarcinoma cells (MCF-7) and normal Chinese hamster ovary cells (CHO) has been found to enhance cellular uptake of Photofrin, which reduces effective dose and exposure time diminishing side effects of the therapy [30]. The efficacy of PDT is also affected by combining with some other drugs, such as Celecoxib, Dihydroartemisinin (DHA), and microRNAs (miRs), which regulate either the signaling pathway or gene expression in some cancer cell lines [31,32,33]. For example, overexpression of miR-130a could theoretically lead to more efficient PDT in resistant cell lines affecting adaptation to ROS stress, such as decreasing the expression of Sirtuin protein family, which regulates FOXO3a/Bim pathway and participates in a lot of neurodegenerative disorders [33,34,35].…”

“…The efficacy of PDT is also affected by combining with some other drugs, such as Celecoxib, Dihydroartemisinin (DHA), and microRNAs (miRs), which regulate either the signaling pathway or gene expression in some cancer cell lines [31,32,33]. For example, overexpression of miR-130a could theoretically lead to more efficient PDT in resistant cell lines affecting adaptation to ROS stress, such as decreasing the expression of Sirtuin protein family, which regulates FOXO3a/Bim pathway and participates in a lot of neurodegenerative disorders [33,34,35]. An upconversion nanoparticle-Zinc phthalocyanine based nanophotosensitizer for PDT has been proven to result in the high 1 O 2 production, leading to a secure and efficient PDT treatment [36].…”